Table of Contents Author Guidelines Submit a Manuscript
The Scientific World Journal
Volume 2014, Article ID 953451, 35 pages
http://dx.doi.org/10.1155/2014/953451
Review Article

Antitumor Activity of Monoterpenes Found in Essential Oils

1Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-970 João Pessoa, PB, Brazil
2Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, Caixa Postal 5009, 58015-970 João Pessoa, PB, Brazil
3Departamento de Farmácia, Universidade Federal de Sergipe, 49100-000 São Cristóvão, SE, Brazil

Received 11 April 2014; Revised 16 June 2014; Accepted 17 June 2014; Published 14 October 2014

Academic Editor: Chantal Pichon

Copyright © 2014 Marianna Vieira Sobral et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: the next generation,” Cell, vol. 144, no. 5, pp. 646–674, 2011. View at Publisher · View at Google Scholar
  2. Brasil Ministério da Saúde and Instituto Nacional de Câncer, Políticas e Ações para Prevenção do Câncer no Brasil Alimentação, Nutrição e Atividade Física, INCA, Rio de Janeiro, Brazil, 2009.
  3. J. C. L. R. Pita, A. L. Xavier, T. K. G. de Sousa et al., “In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana,” Molecules, vol. 17, no. 8, pp. 9573–9589, 2012. View at Publisher · View at Google Scholar
  4. T. Efferth, “Cancer therapy with natural products and medicinal plants,” Planta Medica, vol. 76, pp. 1035–1036, 2010. View at Publisher · View at Google Scholar
  5. D. P. De Sousa, Medicinal Essential Oils: Chemical, Pharmacological and Therapeutic Aspects, Nova Science Publishers, New York, NY, USA, 1st edition, 2012.
  6. P. Rasoanaivo, R. F. Randriana, F. Maggi et al., “Chemical composition and biological activities of the essential oil of Athanasia brownie Hochr. (Asteraceae) endemic to Madagascar,” Chemistry & Biodiversity, vol. 10, no. 10, pp. 1876–1886, 2013. View at Publisher · View at Google Scholar
  7. B. Zapata, L. G. Betancur, C. Duran, and E. Stashenko, “Cytotoxic activity of Asteraceae and Verbenaceae family essential oils,” Journal of Essential Oil Research, vol. 6, pp. 50–57, 2014. View at Google Scholar
  8. S. P. Piaru, R. Mahmud, A. M. S. A. Majid, S. Ismail, and C. N. Man, “Chemical composition, antioxidant and cytotoxicity activities of the essential oils of Myristica fragrans and Morinda citrifolia,” Journal of the Science of Food and Agriculture, vol. 92, pp. 593–597, 2012. View at Publisher · View at Google Scholar
  9. R. P. C. Ferraz, D. S. Bomfim, N. C. Carvalho et al., “Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae),” Phytomedicine, vol. 20, pp. 615–621, 2013. View at Google Scholar
  10. F. F. Maggi, R. F. Randriana, P. Rasoanaivo et al., “Chemical composition and in vitro biological activities of the essential oil of Vepris macrophylla (BAKER) I.VERD. endemic to Madagascar,” Chemistry & Biodiversity, vol. 10, no. 3, pp. 356–365, 2013. View at Google Scholar
  11. M. Nikolić, J. Glamočlija, I. C. F. R. Ferreira et al., “Chemical composition, antimicrobial, antioxidant and antitumor activity of Thymus serpyllum L., Thymus algeriensis Boiss. and Reut and Thymus vulgaris L. essential oils,” Industrial Crops and Products, vol. 52, pp. 183–190, 2014. View at Publisher · View at Google Scholar
  12. D. D. Deb, G. Parimala, D. S. Saravana, and T. Chakraborty, “Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60,” Chemico-Biological Interactions, vol. 193, no. 1, pp. 97–106, 2011. View at Publisher · View at Google Scholar
  13. W. S. Itani, S. H. El-Banna, S. B. Hassan, R. L. Larsson, A. Gali-Muhtasib, and H. U, “Anti-colon cancer components from Lebanese sage (Salvia libanotica) essential oil: mechanistic basis,” Cancer Biology & Therapy, vol. 7, pp. 1765–1773, 2008. View at Google Scholar
  14. A. J. Hayes, D. N. Leach, J. L. Markham, and B. Markovic, “In vitro cytotoxicity of Australian tea tree oil using human cell lines,” Journal of Essential Oil Research, vol. 9, pp. 575–582, 1997. View at Publisher · View at Google Scholar
  15. I. Lampronti, A. M. Saab, and R. Gambari, “Antiproliferative activity of essential oils derived from plants belonging to the Magnoliophyta division,” International Journal of Oncology, vol. 29, pp. 989–995, 2006. View at Google Scholar
  16. S. B. Hassan, H. Gali-Muhtasib, H. Goeransson, and R. Larsson, “Alpha terpineol: a potential anticancer agent which acts through suppressing NF-κB signalling,” Anticancer Research, vol. 30, pp. 1911–1919, 2010. View at Google Scholar
  17. K. Okamura, S. Iwakami, and T. Matsunaga, “Biological activity of monoterpenes from trees,” Toyama-Ken Yakuji Kenkyusho Nenpo, vol. 20, pp. 95–101, 1993. View at Google Scholar
  18. H. F. Lu, J. Y. Liu, S. C. Hsueh et al., “(−)-Menthol inhibits WEHI-3 leukemia cells in vitro and in vivo,” In Vivo, vol. 21, no. 2, pp. 285–289, 2007. View at Google Scholar
  19. J. P. Lin, H. F. Lu, J. H. Lee et al., “Menthol inhibits DNA topoisomerases I, II alpha and beta and promotes NF-kappaB expression in human gastric cancer SNU-5 cells,” Anticancer Res, vol. 25, pp. 2069–2074, 2005. View at Google Scholar
  20. E. J. Park, S. H. Kim, B. J. Kim, S. Y. Kim, I. So, and J. H. Jeon, “Menthol enhances an antiproliferative activity of 1α,25-dihydroxyvitamin D3 in LNCaP cells,” Journal of Clinical Biochemistry and Nutrition, vol. 44, no. 2, pp. 125–130, 2009. View at Google Scholar
  21. Y. Wang, X. Wang, Z. Yang, G. Zhu, D. Chen, and Z. Meng, “Menthol inhibits the proliferation and motility of prostate cancer DU145 cells,” Pathology Oncology Research, vol. 18, no. 4, pp. 903–910, 2005. View at Google Scholar
  22. Q. Li, X. Wang, Z. Yang, B. Wang, and S. Li, “Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24,” Oncology, vol. 77, no. 6, pp. 335–341, 2009. View at Publisher · View at Google Scholar
  23. Y. Okamoto, T. Ohkubo, T. Ikebe, and J. Yamazaki, “Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines,” International Journal of Oncology, vol. 40, pp. 1431–1440, 2012. View at Google Scholar
  24. E. Matsumura, Y. Morita, T. Date et al., “Cytotoxicity of the hinokitiol-related compounds, γ-thujaplicin and β-dolabrin,” Biological & Pharmaceutical Bulletin, vol. 24, pp. 299–302, 2001. View at Google Scholar
  25. Y. Morita, E. Matsumura, H. Tsujibo et al., “Biological activity of a-thujaplicin, the minor component of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino,” Biological & Pharmaceutical Bulletin, vol. 24, pp. 607–611, 2001. View at Google Scholar
  26. D. Slamenova, E. Horvathova, L. Wsolova, M. Sramkova, and J. Navarova, “Investigation of anti-oxidative, cytotoxic, DNA-damaging and DNA-protective effects of plant volatiles eugenol and borneol in human-derived HepG2, Caco-2 and VH10 cell lines,” Mutation Research, vol. 677, no. 1-2, pp. 46–52, 2009. View at Google Scholar
  27. J. Su, H. Lai, J. Chen et al., “Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activationof ROS-mediated DNA damage,” PLoS ONE, vol. 8, Article ID e63502, 2013. View at Google Scholar
  28. T. Efferth, A. Olbrich, A. Sauerbrey, D. D. Ross, E. Gebhart, and M. Neugebauer, “Activity of ascaridol from the anthelmintic herb Chenopodium anthelminticum L. against sensitive and multidrug—resistant tumor cells,” Anticancer Research, vol. 22, pp. 4221–4224, 2002. View at Google Scholar
  29. D. P. Bezerra, J. D. B. Marinho Filho, A. P. N. N. Alves et al., “Antitumor activity of the essential oil from the leaves of Croton regelianus and its component ascaridole,” Chemistry & Biodiversity, vol. 6, pp. 1224–1231, 2009. View at Google Scholar
  30. S. R. Gedara, “Terpenoid content of the leaves of Thymus algeriensis Boiss,” Mansoura Journal of Pharmaceutical Sciences, vol. 24, pp. 133–143, 2008. View at Google Scholar
  31. A. Jaafari, H. Ait Mouse, E. M. Rakib et al., “Chemical composition and antitumor activity of different wild varieties of Moroccan thyme,” Revista Brasileira de Farmacognosia, vol. 17, pp. 477–491, 2007. View at Google Scholar
  32. E. Horvathova, M. Sramkova, J. Labaj, and D. Slamenovam, “Study of cytotoxic, genotoxic and DNA-protective effects of selected plant essential oils on human cells cultured in vitro,” Neuroendocrinology Letters, vol. 27, pp. 44–47, 2006. View at Google Scholar
  33. E. Horvathova, V. Turcaniova, and D. Slamenova, “Comparative study of DNA-damaging and DNA-protective effects of selected components of essential plant oils in human leukemic cells K562,” Neoplasma, vol. 54, pp. 478–483, 2007. View at Google Scholar
  34. D. Slamenova, E. Horvathova, M. Sramkova, and L. Marsalkova, “DNA-protective effects of two components of essential plant oils carvacrol and thymol on mammalian cells cultured in vitro,” Neoplasma, vol. 54, pp. 108–112, 2007. View at Google Scholar
  35. A. Stammati, P. Bonsi, F. Zucco, R. Moezelaar, H.-L. Alakomi, and A. von Wright, “Toxicity of selected plant volatiles in microbial and mammalian short-term assays,” Food and Chemical Toxicology, vol. 37, no. 8, pp. 813–823, 1999. View at Publisher · View at Google Scholar
  36. Q. H. Yin, F. X. Yan, X. Y. Zu et al., “Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2,” Cytotechnology, vol. 64, pp. 43–51, 2012. View at Publisher · View at Google Scholar
  37. K. M. Arunasree, “Anti-proliferative effects of carvacrol on a human metastatic breast cancer cell line, MDA-MB 231,” Phytomedicine, vol. 17, no. 8-9, pp. 581–588, 2010. View at Publisher · View at Google Scholar
  38. S. Jayakumar, A. Madankumar, S. Asokkumar et al., “Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats,” Molecular and Cellular Biochemistry, vol. 360, pp. 51–60, 2012. View at Google Scholar
  39. A. Jaafari, H. A. Mouse, L. A. M'Bark et al., “Differential antitumor effect of essential oils and their major components of Thymus broussonettii: relationship to cell cycle and apoptosis induction,” Herba Polonica Journal, vol. 55, pp. 36–50, 2009. View at Google Scholar
  40. H. Zeytinoglu, Z. Incesu, and K. H. C. Baser, “Inhibition of DNA synthesis by carvacrol in mouse myoblast cells bearing a human N-RAS oncogene,” Phytomedicine, vol. 10, pp. 292–299, 2003. View at Google Scholar
  41. E. Ipek, H. Zeytinoglu, S. Okay, B. A. Tuylu, M. Kurkcuoglu, and K. H. C. Baser, “Genotoxicity and antigenotoxicity of Origanum oil and carvacrol evaluated by Ames Salmonella/microsomal test,” Food Chemistry, vol. 93, no. 3, pp. 551–556, 2005. View at Publisher · View at Google Scholar
  42. A. Ozkan and A. Erdogan, “A comparative evaluation of antioxidant and anticancer activity of essential oil from Origanum onites (Lamiaceae) and its two major phenolic components,” Turkish Journal of Biology, vol. 35, pp. 735–742, 2011. View at Google Scholar
  43. M. Zeytinoglu, S. Aydin, Y. Ozturk, K. Husnu, and C. Baser, “Inhibitory effects of carvacrol on DMBA induced pulmonary tumorigenesis in rats,” Acta Pharmaceutica Turcica, vol. 40, no. 2, pp. 93–98, 1998. View at Google Scholar
  44. C. Hirobe, Z. S. Qiao, K. Takeya, and H. Itokawa, “Cytotoxic principles from Majorana syriaca,” Nature Medicine, vol. 52, pp. 74–77, 1998. View at Google Scholar
  45. A. Paramasivam, S. Sambantham, J. Shabnam et al., “Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP,” Toxicology Letters, vol. 213, pp. 151–159, 2012. View at Google Scholar
  46. A. Jaafari, M. Tilaoui, H. A. Ait Mouse et al., “Comparative study of the antitumor effect of natural monoterpenes: relationship to cell cycle analysis,” Revista Brasileira de Farmacognosia, vol. 22, pp. 534–540, 2012. View at Google Scholar
  47. S. Ivankovic, R. Stojkovic, M. Jukic, M. Milos, and M. Jurin, “The antitumor activity of thymoquinone and thymohydroquinone in vitro and in vivo,” Experimental Oncology, vol. 28, pp. 220–224, 2006. View at Google Scholar
  48. H. A. Johnson, L. L. Rogers, M. L. Alkire, T. G. McCloud, and J. L. McLaughlin, “Bioactive monoterpenes from Monarda fistulosa (Lamiaceae),” Natural Product Letters, vol. 11, no. 4, pp. 241–250, 1998. View at Publisher · View at Google Scholar
  49. S. Rooney and M. F. Ryan, “Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines,” Anticancer Research, vol. 25, pp. 2199–2204, 2005. View at Google Scholar
  50. S. Bourgou, A. Pichette, B. Marzouk, and J. Legault, “Bioactivities of black cumin essential oil and its main terpenes from Tunisia,” South African Journal of Botany, vol. 76, pp. 210–216, 2010. View at Publisher · View at Google Scholar
  51. V. Cecarini, L. Quassinti, A. di Blasio et al., “Effects of thymoquinone on isolated and cellular proteasomes,” FEBS Journal, vol. 277, pp. 2128–2141, 2010. View at Google Scholar
  52. S. H. Jafri, J. Glass, R. Shi, S. Zhang, M. Prince, and H. Kleiner-Hancock, “Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo,” Journal of Experimental & Clinical Cancer Research, vol. 29, p. 87, 2010. View at Google Scholar
  53. O. A. Badary, M. N. Nagi, O. A. al-Shabanah, H. A. al-Sawaf, M. O. al-Sohaibani, and A. M. al-Bekairi, “Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity,” Canadian Journal of Physiology and Pharmacology, vol. 75, pp. 1356–1361, 1997. View at Publisher · View at Google Scholar
  54. O. A. Badary, “Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice,” Journal of Ethnopharmacology, vol. 67, no. 2, pp. 135–142, 1999. View at Publisher · View at Google Scholar
  55. S. Banerjee, A. O. Kaseb, Z. Wang et al., “Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer,” Cancer Research, vol. 69, pp. 5575–5583, 2009. View at Publisher · View at Google Scholar
  56. G. Sethi, K. S. Ahn, and B. B. Aggarwal, “Targeting nuclear factor-κB activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis,” Molecular Cancer Research, vol. 6, no. 6, pp. 1059–1070, 2008. View at Publisher · View at Google Scholar
  57. H. Gali-Muhtasib, D. Kuester, C. Mawrin et al., “Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells,” Cancer Research, vol. 68, pp. 5609–5618, 2008. View at Publisher · View at Google Scholar
  58. F. Li, P. Rajendran, and G. Sethi, “Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway,” British Journal of Pharmacology, vol. 161, no. 3, pp. 541–554, 2010. View at Google Scholar
  59. O. A. Badary and A. M. G. El-Din, “Antitumor activity of thymoquinone against fibrosarcoma tumorigenesis,” Cancer Molecular Biology, vol. 7, no. 3, pp. 1515–1526, 2000. View at Google Scholar
  60. O. A. Badary and E. A. M. Gamal, “Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis,” Cancer Detection and Prevention, vol. 25, pp. 362–368, 2001. View at Google Scholar
  61. J. Barron, H. Benghuzzi, and M. Tucci, “Effects of thymoquinone and selenium on the proliferation of MG 63 cells in tissue culture,” Biomedical Sciences Instrumentation, vol. 44, pp. 434–440, 2008. View at Google Scholar
  62. M. Roepke, A. Diestel, K. Bajbouj et al., “Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells,” Cancer Biology & Therapy, vol. 6, pp. 160–169, 2007. View at Google Scholar
  63. L. Peng, A. Liu, Y. Shen et al., “Antitumorandanti-angiogenesis effects ofthymoquinoneon osteosarcoma through the NF-κB pathway,” Oncology Reports, vol. 29, pp. 571–578, 2013. View at Google Scholar
  64. L. S. Yazan, W. K. Ng, G. Al-Naqeeb, and M. Ismail, “Cytotoxicity of thymoquinone (TQ) from Nigella sativa towards human cervical carcinoma cells (HeLa),” Journal of Pharmacy Research, vol. 2, pp. 585–589, 2009. View at Google Scholar
  65. N. El-Najjar, M. Chatila, H. Moukadem et al., “Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling,” Apoptosis, vol. 15, pp. 183–195, 2010. View at Publisher · View at Google Scholar
  66. F. Wilson-Simpson, S. Vance, and H. Benghuzzi, “Physiological responses of ES-2 ovarian cell line following administration of epigallocatechin-3-gallate (EGCG), thymoquinone (TQ), and selenium (SE),” Biomedical Sciences Instrumentation, vol. 43, pp. 378–383, 2007. View at Google Scholar
  67. N. Farah, H. Benghuzzi, M. Tucci, and Z. Cason, “The effects of isolated antioxidants from black seed on the cellular metabolism of A549 cells,” Biomedical Sciences Instrumentation, vol. 41, pp. 211–216, 2005. View at Google Scholar
  68. H. Zubair, H. Y. Khan, A. Sohail et al., “Redox cycling of endogenous copper bythymoquinoneleads to ROS-mediated DNA breakage and consequent cell death: putativeanticancermechanism of antioxidants,” Cell Death & Disease, vol. 4, p. e660, 2013. View at Google Scholar
  69. W. H. Talib and M. M. Abu Khader, “Combinatorial effects ofthymoquinoneon theanticanceractivityand hepatotoxicity of the prodrug CB 1954,” Scientia Pharmaceutica, vol. 81, pp. 519–530, 2013. View at Publisher · View at Google Scholar
  70. L. R. Richards, P. Jones, J. Hughes, H. Benghuzzi, and M. Tucci, “LNCaP cells exposed to ceramic drug delivery treatment with epigallocatechin-3-gallate, thymoquinone, and tannic acid,” Biomedical Sciences Instrumentation, vol. 43, pp. 242–247, 2007. View at Google Scholar
  71. L. R. Richards, P. Jones, H. Benghuzzi, and M. Tucci, “A comparison of the morphological changes associated with conventional and sustained treatment with epigallocatechin-3-gallate, thymoquinone, and tannic acid on LNCaP cells,” Biomedical Sciences Instrumentation, vol. 44, pp. 465–470, 2008. View at Google Scholar
  72. M. A. El-Mahdy, Q. Zhu, Q. Wang, G. Wani, and A. A. Wani, “Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells,” International Journal of Cancer, vol. 117, pp. 409–417, 2005. View at Google Scholar
  73. P. S. Koka, D. Mondal, M. Schultz, A. B. Abdel-Mageed, and K. C. Agrawal, “Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species,” Experimental Biology and Medicine, vol. 235, pp. 751–760, 2010. View at Google Scholar
  74. A. M. Shoieb, M. Elgayyar, P. S. Dudrick, J. L. Bell, and P. K. Tithof, “In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone,” International Journal of Oncology, vol. 22, pp. 107–113, 2003. View at Google Scholar
  75. S. A. Hassan, W. A. Ahmed, F. M. Galeb, M. A. El-Taweel, and F. A. Abu-Bedair, “In vitro challenge using thymoquinone on hepatocellular carcinoma (HepG2) cell line,” Iranian Journal of Pharmaceutical Research, vol. 7, pp. 283–290, 2008. View at Google Scholar
  76. H. U. Gali-Muhtasib, W. G. A. Kheir, L. A. Kheir, N. Darwiche, and P. A. Crooks, “Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes,” Anticancer Drugs, vol. 15, pp. 389–399, 2004. View at Google Scholar
  77. R. L. Gurung, S. N. Lim, A. K. Khaw et al., “Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells,” PLoS ONE, vol. 5, Article ID e12124, 2010. View at Google Scholar
  78. H. Satooka and I. Kubo, “Effects of thymol on B16-F10 melanoma cells,” Journal of Agricultural and Food Chemistry, vol. 60, pp. 2746–2752, 2012. View at Google Scholar
  79. A. Abusnina, M. Alhosin, T. Keravis et al., “Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis,” Cellular Signalling, vol. 23, pp. 152–160, 2011. View at Google Scholar
  80. M. P. Torres, M. P. Ponnusamy, S. Chakraborty et al., “Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies,” Molecular Cancer Therapeutics, vol. 9, pp. 1419–1431, 2010. View at Google Scholar
  81. D. R. Worthen, O. A. Ghosheh, and P. A. Crooks, “The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L.,” Anticancer Research, vol. 18, pp. 1527–1532, 1998. View at Google Scholar
  82. A. el-SA, Q. Zhu, Z. I. Shah et al., “Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells,” Mutation Research, vol. 706, no. 1-2, pp. 28–35, 2011. View at Google Scholar
  83. J. Ravindran, H. B. Nair, B. Sung, S. Prasad, R. R. Tekmal, and B. B. Aggarwal, “Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential,” Biochemical Pharmacology, vol. 79, no. 11, pp. 1640–1647, 2010. View at Publisher · View at Google Scholar
  84. G. M. Ganea, S. O. Fakayode, J. N. Losso, C. F. Van Nostrum, C. M. Sabliov, and I. M. Warner, “Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles,” Nanotechnology, vol. 21, no. 28, Article ID 285104, 2010. View at Google Scholar
  85. A. Wirries, S. Breyer, K. Quint, R. Schobert, and M. Ocker, “Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells,” Experimental and Therapeutic Medicine, vol. 1, pp. 369–375, 2010. View at Google Scholar
  86. S. Banerjee, A. S. Azmi, S. Padhye et al., “Structure-activity studies on therapeutic potential of thymoquinone analogs in pancreatic cancer,” Pharmaceutical Research, vol. 27, pp. 1146–1158, 2010. View at Publisher · View at Google Scholar
  87. K. Effenberger, S. Breyer, and R. Schobert, “Terpene conjugates of the Nigella sativa seed-oil constituent thymoquinone with enhanced efficacy in cancer cells,” Chemistry & Biodiversity, vol. 7, pp. 129–139, 2010. View at Google Scholar
  88. N. El-Najjar, R. Ketola, T. A et al., “Impact of protein binding on the analytical detectability and anticancer activity of thymoquinone,” The Journal of Biological Chemistry, vol. 4, pp. 97–107, 2011. View at Google Scholar
  89. O. A. Al-Shabanah, O. A. Badary, M. N. Nagi, N. M. Al-Gharably, A. C. Al-Rikabi, and A. M. Al-Bekairi, “Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity,” Journal of Experimental & Clinical Cancer Research, vol. 17, no. 2, pp. 193–198, 1998. View at Google Scholar
  90. M. N. Nagi and H. A. Almakki, “Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: possible role in protection against chemical carcinogenesis and toxicity,” Phytotherapy Research, vol. 23, pp. 1295–1298, 2009. View at Publisher · View at Google Scholar
  91. Y. Li, C. Yeung, L. C. M. Chiu, Y. Cen, and V. E. C. Ooi, “Chemical composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Schefflera heptaphylla,” Phytotherapy Research, vol. 23, no. 1, pp. 140–142, 2009. View at Publisher · View at Google Scholar
  92. S. Rajput, B. N. Kumar, K. K. Dey, I. Pal, A. Parekh, and M. Mandal, “Molecular targeting of Akt by thymoquinone promotes G1 arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells,” Life Sciences, vol. 93, pp. 783–790, 2013. View at Publisher · View at Google Scholar
  93. K. Effenberger-Neidnicht and R. Schobert, “Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin,” Cancer Chemotherapy and Pharmacology, vol. 67, pp. 867–874, 2011. View at Google Scholar
  94. R. Tundis, M. R. Loizzo, M. Bonesi et al., “In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines,” Natural Products Research, vol. 23, no. 18, pp. 1707–1718, 2009. View at Google Scholar
  95. M. L. Salem, F. Q. Alenzi, and W. Y. Attia, “Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigen-specific CD8-positive T cells in vitro,” British Journal of Biomedical Science, vol. 68, no. 3, pp. 131–137, 2011. View at Google Scholar
  96. S. Attoub, O. Sperandio, H. Raza et al., “Thymoquinoneas an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo,” Fundamental & Clinical Pharmacology, vol. 27, pp. 557–569, 2013. View at Google Scholar
  97. M. Lang, M. Borgmann, G. Oberhuber et al., “Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling,” Molecular Cancer, vol. 12, p. 41, 2013. View at Publisher · View at Google Scholar
  98. E. Abdelfadil, Y. Cheng, D. Bau et al., “Thymoquinone induces apoptosis in oral câncer cells through P38β Inhibition,” The American Journal of Chinese Medicine, vol. 41, pp. 683–696, 2013. View at Publisher · View at Google Scholar
  99. F. Odeh, S. I. Ismail, R. Abu-Dahab, I. S. Mahmoud, and A. Al Bawab, “Thymoquinonein liposomes: a study of loading efficiency and biological activity towards breast cancer,” Drug Delivery, vol. 19, pp. 371–377, 2012. View at Publisher · View at Google Scholar
  100. S. Das, K. K. Dey, G. Dey et al., “Antineoplasticand apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma,” PLoS ONE, vol. 7, Article ID e46641, 2012. View at Publisher · View at Google Scholar
  101. M. Alhosin, A. Ibrahim, A. Boukhari et al., “Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts,” Investigational New Drugs, vol. 30, pp. 1813–1819, 2012. View at Google Scholar
  102. M. M. Saleh, F. A. Hashem, and K. W. Glombitza, “Cytotoxicity and in vitro effects on human cancer cell lines of volatiles of Apium graveolens var. filicinum,” Pharmaceutical & Pharmacological Letters, vol. 8, pp. 97–99, 1998. View at Google Scholar
  103. S. L. Silva, P. M. Figueiredo, and T. Yano, “Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. Leaves,” Acta Amazonica, vol. 37, pp. 281–286, 2007. View at Google Scholar
  104. J. A. Elegbede, T. H. Maltzman, C. E. Elson, and M. N. Gould, “Effects of anticarcinogenic monoterpenes on phase II hepatic metabolizing enzymes,” Carcinogenesis, vol. 14, no. 6, pp. 1221–1223, 1993. View at Publisher · View at Google Scholar
  105. P. L. Crowell, A. S. Ayoubi, and Y. D. Burke, “Antitumorigenic effects of limonene and perillyl alcohol against pancreatic and breast cancer,” in Dietary Phytochemicals in Cancer Prevention and Treatment, vol. 401 of Advances in Experimental Medicine and Biology, pp. 131–136, Springer, New York, NY, USA, 1996. View at Publisher · View at Google Scholar
  106. A. Sonboli, M. A. Esmaeili, A. Gholipour, and M. Kanani, “Composition, cytotoxicity and antioxidant activity of the essential oil of Dracocephalum surmandinum from Iran,” Natural Product Communications, vol. 5, pp. 341–344, 2010. View at Google Scholar
  107. M. H. Gelb, F. Tamanoi, K. Yokoyama, F. Ghomashchi, K. Esson, and M. N. Gould, “The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol,” Cancer Letters, vol. 91, no. 2, pp. 169–175, 1995. View at Publisher · View at Google Scholar
  108. C. A. Manassero, J. R. Girotti, S. Mijailovsky, M. García de Bravo, and M. Polo, “In vitro comparative analysis of antiproliferative activity of essential oil from mandarin peel and its principal component limonene,” Natural Product Research, vol. 2, pp. 1475–1478, 2013. View at Google Scholar
  109. B. Bhattacharjee and J. Chatterjee, “Identification of proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of essential oils in cardamom by dual reverse virtual screening and binding pose analysis,” Asian Pacific Journal of Cancer Prevention, vol. 14, pp. 3735–3742, 2013. View at Google Scholar
  110. J. Ji, L. Zhang, Y. Wu, X. Zhu, S. Lv, and X. Sun, “Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells,” Leukemia & Lymphoma, vol. 47, pp. 2617–2624, 2006. View at Google Scholar
  111. T. Kawamori, T. Tanaka, Y. Hirose, M. Ohnishi, and H. Mori, “Inhibitory effects of d-limonene on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats,” Carcinogenesis, vol. 17, no. 2, pp. 369–372, 1996. View at Google Scholar
  112. M. Pattanayak, P. K. Seth, S. Smita, and S. K. Gupta, “Geraniol and limonene interaction with 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase for their role as cancer chemo-preventive agents,” Journal of Proteomics & Bioinformatics, vol. 2, pp. 466–474, 2009. View at Publisher · View at Google Scholar
  113. X. Chen, O. Shuzo, Y. Li, and R. Han, “Effect of d-limonene, Salvia miltiorrhiza and turmeric derivatives on membrane association and gap junction intercellular communication of ras gene product,” Yao Xue Xue Bao, vol. 33, pp. 821–827, 1998. View at Google Scholar
  114. J. D. Haag, M. J. Lindstrom, and M. N. Gould, “Limonene-induced regression of mammary carcinomas,” Cancer Research, vol. 52, no. 14, pp. 4021–4026, 1992. View at Google Scholar
  115. S. K. Chander, A. G. B. Lansdown, Y. A. Luqmani et al., “Effectiveness of combined limonene and 4-hydroxy androstenedione in the treatment of NMU-induced rat mammary tumors,” The British Journal of Cancer, vol. 69, pp. 879–882, 1994. View at Google Scholar
  116. C. E. Elson, T. H. Maltzman, J. L. Boston, M. A. Tanner, and M. N. Gould, “Anti-carcinogenic activity of d-limonene during the initiation and promotion/progression stages of DMBA-induced rat mammary carcinogenesis,” Carcinogenesis, vol. 9, pp. 331–332, 1988. View at Google Scholar
  117. K. N. M. Chidambara, G. K. Jayaprakasha, M. Shivappa, and B. S. P. Mantur, “Citrus monoterpenes: potential source of phytochemicals for cancer prevention,” in Emerging Trends in Dietary Components for Preventing and Combating Disease, pp. 545–558, 2010. View at Google Scholar
  118. M. G. Manuele, G. Ferraro, and C. Anesini, “Effect of Tilia x viridis flower extract on the proliferation of a lymphoma cell line and on normal murine lymphocytes: contribution of monoterpenes, especially limonene,” Phytotherapy Research, vol. 22, pp. 1520–1526, 2008. View at Google Scholar
  119. T. J. Raphael and G. Kuttan, “Preliminary study of antimetastatic activity of naturally occurring monoterpene limonene,” Amala Research Bulletin, vol. 23, pp. 99–106, 2003. View at Google Scholar
  120. M. A. Morse and A. L. Toburen, “Inhibition of metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by limonene,” Cancer Letters, vol. 104, pp. 211–217, 1996. View at Google Scholar
  121. J. A. Elegbede and M. N. Gould, “Monoterpenes reduced adducts formation in rats exposed to aflatoxin B1,” African Journal of Biotechnology, vol. 1, pp. 46–49, 2002. View at Google Scholar
  122. G. Q. Zheng, P. M. Kenney, and L. K. T. Lam, “Potential anticarcinogenic natural products isolated from lemongrass oil and galanga root oil,” Journal of Agricultural and Food Chemistry, vol. 41, pp. 153–156, 1993. View at Google Scholar
  123. T. Parija and B. Ranjan, “Involvement of YY1 and its correlation with c-myc in NDEA induced hepatocarcinogenesis, its prevention by d-limonene,” Molecular Biology Reports, vol. 30, no. 1, pp. 41–46, 2003. View at Google Scholar
  124. G. Q. Zheng, J. Zhang, P. M. Kenney, and L. K. T. Lam, “Stimulation of glutathione S-transferase and inhibition of carcinogenesis in mice by celery seed oil constituents,” ACS Symposium Series, vol. 546, pp. 230–238, 1994. View at Google Scholar
  125. L. Yeruva, K. J. Pierre, A. Elegbede, R. C. Wang, and S. W. Carper, “Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non-small cell lung cancer cells,” Cancer Letters, vol. 257, pp. 216–226, 2007. View at Google Scholar
  126. D. Samaila, B. J. Toy, C. Wang Robert, and A. Elegbede, “Monoterpenes enhanced the sensitivity of head and neck cancer cells to radiation treatment in vitro,” Anticancer Research, vol. 24, no. 5, pp. 3089–3095, 2004. View at Google Scholar
  127. J. M. Stark, Y. D. Burke, J. H. McKinzie, S. A. Ayoubi, and P. L. Crowell, “Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol,” Cancer Letters, vol. 96, no. 1, pp. 15–21, 1995. View at Google Scholar
  128. Y. D. Burke, M. J. Stark, S. L. Roach, S. E. Sen, and P. L. Crowell, “Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol,” Lipids, vol. 32, no. 2, pp. 151–156, 1997. View at Publisher · View at Google Scholar
  129. K. R. Stayrook, J. H. Mckinzie, L. H. Barbhaiya, and P. L. Crowell, “Effects of the antitumor agent perillyl alcohol on H-Ras vs. K-Ras farnesylation and signal transduction in pancreatic cells,” Anticancer Research, vol. 18, pp. 823–828, 1998. View at Google Scholar
  130. K. R. Stayrook, J. H. Mckinzie, Y. D. Burke, Y. A. Burke, and P. L. Crowell, “Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells,” Carcinogenesis, vol. 18, pp. 1655–1658, 1997. View at Google Scholar
  131. I. V. Lebedeva, Z. Su, N. Vozhilla et al., “Chemoprevention by perillyl alcohol coupled with viral gene therapy reduces pancreatic cancer pathogenesis,” Molecular Cancer Therapeutics, vol. 7, pp. 2042–2050, 2008. View at Google Scholar
  132. T. Sundin, D. M. Peffley, D. Gauthier, and P. Hentosh, “The isoprenoid perillyl alcohol inhibits telomerase activity in prostate câncer cells,” Biochimie, vol. 94, pp. 2639–2648, 2012. View at Google Scholar
  133. Y. Chen and D. Hu, “Effects of POH in combination with STI571 on the proliferation and apoptosis of K562 cells,” Journal of Huazhong University of Science and Technology [Medical Sciences], vol. 24, pp. 41–44, 2004. View at Google Scholar
  134. S. S. Clark, “Perillyl alcohol Iinduces c-Myc-dependent apoptosis in Bcr/Abl-transformed leukemia cells,” Oncology, vol. 70, pp. 13–18, 2006. View at Google Scholar
  135. H. Loutrari, M. Hatziapostolou, V. Skouridou et al., “Perillyl alcohol is an angiogenesis inhibitor,” Journal of Pharmacology and Experimental Therapeutics, vol. 311, pp. 568–575, 2004. View at Publisher · View at Google Scholar
  136. H. Loutrari, V. Skouridou, F. N. Kolisis, C. Roussos, and A. Papapetropoulos, “Perillyl alcohol attenuates in vitro angiogenesis, modulates angiogenic factor production and inhibits cell proliferation and survival in endothelial and tumour cells,” Epitheorese Klinikes Farmakologias kai Farmakokinetikes, vol. 18, pp. 30–32, 2004. View at Google Scholar
  137. D. G. Garcia, L. M. F. Amorim, F. M. V. Castro et al., “The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor,” Molecular and Cellular Biochemistry, vol. 345, pp. 29–34, 2010. View at Google Scholar
  138. P. L. Crowell, Z. Ren, S. Lin, E. Vedejs, and M. N. Gould, “Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation,” Biochemical Pharmacology, vol. 47, pp. 1405–1415, 1994. View at Publisher · View at Google Scholar
  139. M. B. Sahin, S. M. Perman, G. Jenkins, and S. S. Clark, “Perillyl alcohol selectively induces G0/G1 arrest and apoptosis in Bcr/Abl-transformed myeloid cell lines,” Leukemia, vol. 13, pp. 1581–1591, 1999. View at Google Scholar
  140. Y. Satomi, S. Miyamoto, and M. N. Gould, “Induction of AP-1 activity by perillyl alcohol in breast cancer cells,” Carcinogenesis, vol. 20, pp. 1957–1961, 1999. View at Google Scholar
  141. J. K. Ahn, C. K. Lee, E. K. Choi, R. Griffin, C. W. Song, and H. J. Park, “Cytotoxicity of perillyl alcohol against cancer cells is potentiated by hyperthermia,” International Journal of Radiation Oncology, Biology, Physics, vol. 57, pp. 813–819, 2003. View at Google Scholar
  142. Z. Ren and M. N. Gould, “Inhibition of ubiquinone and cholesterol synthesis by the monoterpene perillyl alcohol,” Cancer Letters, vol. 76, pp. 185–190, 1994. View at Google Scholar
  143. Z. Ren, C. E. Elson, and M. N. Gould, “Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in NIH3T3 cells,” Biochemical Pharmacology, vol. 54, pp. 113–120, 1997. View at Google Scholar
  144. I. T. Balassiano, S. A. de Paulo, N. H. Silva et al., “Effects of perillyl alcohol in glial C6 cell line in vitro and anti-metastatic activity in chorioallantoic membrane,” International Journal of Molecular Medicine, vol. 10, no. 6, pp. 785–788, 2002. View at Google Scholar
  145. C. O. Da Fonseca, G. Schwartsmann, J. Fischer et al., “Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas,” Surgical Neurology, vol. 70, pp. 259–267, 2008. View at Google Scholar
  146. S. C. Chaudhary, M. S. Alam, M. S. Siddiqui, and M. Athar, “Perillyl alcohol attenuates Ras-ERK signaling to inhibit murine skin inflammation and tumorigenesis,” Chemico-Biological Interactions, vol. 179, pp. 145–153, 2009. View at Google Scholar
  147. E. A. Ariazi, Y. Satomi, M. J. Ellis et al., “Activation of the transforming growth factor β signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol,” Cancer Research, vol. 59, pp. 1917–1928, 1999. View at Google Scholar
  148. S. S. Clark, S. M. Perman, M. B. Sahin, G. J. Jenkins, and J. A. Elegbede, “Antileukemia activity of perillyl alcohol (POH): uncoupling apoptosis from G0/G1 arrest suggests that the primary effect of POH on Bcr/Abl-transformed cells is to induce growth arrest,” Leukemia, vol. 16, pp. 213–222, 2002. View at Publisher · View at Google Scholar
  149. I. V. Lebedeva, Z. Su, N. Vozhilla et al., “Mechanism of in vitro pancreatic cancer cell growth inhibition by melanoma differentiation-associated gene-7/interleukin-24 and perillyl alcohol,” Cancer Research, vol. 68, pp. 7439–7447, 2008. View at Google Scholar
  150. P. J. M. Boon, D. van der Boon, and G. J. Mulder, “Cytotoxicity and biotransformation of the anticancer drug perillyl alcohol in PC12 cells and in the rat,” Toxicology and Applied Pharmacology, vol. 167, pp. 55–62, 2000. View at Google Scholar
  151. L. R. Phillips, L. Malspeis, and J. G. Supko, “Pharmacokinetics of active drug metabolites after oral administration of perillyl alcohol, an investigational antineoplastic agent, to the dog,” Drug Metabolism and Disposition, vol. 23, no. 7, pp. 676–680, 1995. View at Google Scholar
  152. D. Rajesh, R. A. Stenzel, and S. P. Howard, “Perillyl alcohol as a radio-/chemosensitizer in malignant glioma,” The Journal of Biological Chemistry, vol. 278, pp. 35968–35978, 2003. View at Google Scholar
  153. G. H. Ripple, M. N. Gould, J. A. Stewart et al., “Phase I clinical trial of perillyl alcohol administered daily,” Clinical Cancer Research, vol. 4, pp. 1159–1164, 1998. View at Google Scholar
  154. G. H. Ripple, M. N. Gould, R. Z. Arzoomanian et al., “Phase I clinical and pharmacokinetic study of perillyl alcohol administered four times a day,” Clinical Cancer Research, vol. 6, pp. 390–396, 2000. View at Google Scholar
  155. C. G. Azzoli, V. A. Miller, K. N. G. Kenneth et al., “A phase I trial of perillyl alcohol in patients with advanced solid tumors,” Cancer Chemotherapy and Pharmacology, vol. 51, pp. 493–498, 2003. View at Google Scholar
  156. G. R. Hudes, C. E. Szarka, A. Adams et al., “Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies,” Clinical Cancer Research, vol. 6, pp. 3071–3080, 2000. View at Google Scholar
  157. S. M. Meadows, D. Mulkerin, J. Berlin et al., “Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer,” International Journal of Gastrointestinal Cancer, vol. 32, no. 2-3, pp. 125–128, 2002. View at Publisher · View at Google Scholar
  158. W. Wang, N. Li, M. Luo, Y. Zu, and T. Efferth, “Antibacterial activity and anticancer activity of Rosmarinus officinalis L. essential oil compared to that of its main components,” Molecules, vol. 17, no. 3, pp. 2704–2713, 2012. View at Google Scholar
  159. Z. K. Asanova, E. M. Suleimenov, G. A. Atazhanova et al., “Biological activity of 1,8-cineole from levant wormwood,” Pharmaceutical Chemistry Journal, vol. 37, pp. 28–30, 2003. View at Google Scholar
  160. J. Cha, Y. Kim, and J. Kim, “Essential oil and 1, 8-cineole from Artemisia lavandulaefolia induces apoptosis in KB cells via mitochondrial stress and caspase activation,” Food Science and Biotechnology, vol. 19, pp. 185–191, 2010. View at Google Scholar
  161. A. Calcabrini, A. Stringaro, L. Toccacieli et al., “Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells,” Journal of Investigative Dermatology, vol. 122, pp. 349–360, 2004. View at Publisher · View at Google Scholar
  162. G. Bozzuto, M. Colone, L. Toccacieli, A. Stringaro, and A. Molinari, “Tea tree oil might combat melanoma,” Planta Medica, vol. 77, pp. 54–56, 2011. View at Google Scholar
  163. S. J. Greay, D. J. Ireland, H. T. Kissick et al., “Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol,” Cancer Chemotherapy and Pharmacology, vol. 65, pp. 877–888, 2010. View at Google Scholar
  164. N. K. Dubey, K. Takeya, and H. Itokawa, “Citral: a cytotoxic principle isolated from the essential oil of Cymbopogon citratus against P388 leukemia cells,” Current Science, vol. 73, pp. 22–24, 1997. View at Google Scholar
  165. B. S. Wright, A. Bansal, D. M. Moriarity, S. Takaku, and W. N. Setzer, “Cytotoxic leaf essential oils from neotropical Lauraceae: synergistic effects of essential oil components,” Natural Product Communications, vol. 22, pp. 1241–1244, 2007. View at Google Scholar
  166. Y. Liu, R. J. Whelan, B. R. Pattnaik et al., “Terpenoids from Zingiber officinale (ginger) induce apoptosis in endometrial cancercells through the activationof p53,” PLoS ONE, vol. 7, no. 12, Article ID e53178, 2012. View at Publisher · View at Google Scholar
  167. H. Xia, W. Liang, Q. Song, X. Chen, X. Chen, and J. Hong, “The in vitro study of apoptosis in NB4 cell induced by citral,” Cytotechnology, vol. 65, pp. 49–57, 2013. View at Google Scholar
  168. A. Mesa-Arango, J. Monteil-Ramos, B. Zapata, C. Duran, L. Betancur-Galvis, and E. Stashenko, “Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E., Brown, composition, cytotoxicity and antifungal activity,” Memórias do Instituto Oswaldo Cruz, vol. 104, pp. 878–884, 2009. View at Google Scholar
  169. E. Aydin, H. Turkez, and M. S. Kele, “Potential anticancer activity of carvone in N2a neuroblastoma cell line,” Toxicology and Industrial Health, 2013. View at Google Scholar
  170. C. Chaverri, C. Diaz, and J. F. Ciccio, “Leaf essential oil of Manekia naranjoana (Piperaceae) from Costa Rica and its cytotoxic activity,” Natural Product Communications, vol. 6, pp. 145–148, 2011. View at Google Scholar
  171. A. Bansal, D. M. Moriarity, S. Takaku, and W. N. Setzer, “Chemical composition and cytotoxic activity of the leaf essential oil of Ocotea tonduziifrom Monteverde, Costa Rica,” Natural Product Communications, vol. 2, pp. 781–784, 2007. View at Google Scholar
  172. D. Fraternale, D. Ricci, C. Calcabrini, M. Guescini, C. Martinelli, and P. Sestili, “Cytotoxic activity of essential oils of aerial parts and ripe fruits of Echinophora spinosa (Apiaceae),” Natural Product Communications, vol. 8, pp. 1645–1649, 2013. View at Google Scholar
  173. R. A. Cole, A. Bansal, D. M. Moriarity, W. A. Haber, and W. N. Setzer, “Chemical composition and cytotoxic activity of the leaf essential oil of Eugenia zuchowskiae from Monteverde, Costa Rica,” Journal of Natural Medicines, vol. 61, pp. 414–417, 2007. View at Google Scholar
  174. K. Jin, M. Bak, M. Jun, H. Lim, W. Jo, and W. S. Jeong, “α-pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells,” Food Science and Biotechnology, vol. 19, pp. 1325–1332, 2010. View at Google Scholar
  175. S. Carnesecchi, K. Langley, F. Exinger, F. Gosse, and F. Raul, “Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-Fluorouracil treatment,” Journal of Pharmacology and Experimental Therapeutics, vol. 301, no. 2, pp. 625–630, 2002. View at Google Scholar
  176. S. Carnesecchi, R. Bras-Goncalves, A. Bradaia et al., “Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts,” Cancer Letters, vol. 215, no. 1, pp. 53–59, 2004. View at Google Scholar
  177. M. P. Polo and M. G. de Bravo, “Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2,” Biochemistry and Cell Biology, vol. 84, pp. 102–111, 2006. View at Google Scholar
  178. R. Crespo, S. M. Villegas, M. C. Abba, M. G. de Bravo, and M. P. Polo, “Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways,” Biochemistry and Cell Biology, vol. 91, pp. 131–139, 2013. View at Google Scholar
  179. S. Carnesecchi, Y. Schneider, J. Ceraline et al., “Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells,” Journal of Pharmacology and Experimental Therapeutics, vol. 298, pp. 197–200, 2001. View at Google Scholar
  180. T. P. Ong, R. Heidor, A. de Conti, M. L. Z. Dagli, and F. S. Moreno, “Farnesol and geraniol chemopreventive activities during the initial phases of hepatocarcinogenesis involve similar actions on cell proliferation and DNA damage, but distinct actions on apoptosis, plasma cholesterol and HMGCoA reductase,” Carcinogenesis, vol. 27, pp. 1194–1203, 2006. View at Google Scholar
  181. M. T. Cardozo, A. de Conti, T. P. Ong et al., “Chemopreventive effects of β-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA,” The Journal of Nutritional Biochemistry, vol. 22, pp. 130–135, 2011. View at Publisher · View at Google Scholar
  182. A. Madankumar, S. Jayakumar, K. Gokuladhas et al., “Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis,” European Journal of Pharmacology, vol. 705, pp. 148–155, 2013. View at Google Scholar
  183. L. W. Wattenberg, “Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol),” Carcinogenesis, vol. 12, pp. 151–152, 1991. View at Google Scholar
  184. J. M. Cherng, D. E. Shieh, W. Chiang, M. Y. Chang, and L. C. Chiang, “Chemopreventive effects of minor dietary constituents in common foods on human cancer cells,” Bioscience, Biotechnology, and Biochemistry, vol. 71, pp. 1500–1504, 2007. View at Publisher · View at Google Scholar
  185. L. C. Chiang, W. Chiang, M. Y. Chang, L. T. Ng, and C. C. Lin, “Antileukemic activity of selected natural products in Taiwan,” American Journal of Chinese Medicine, vol. 31, pp. 37–46, 2003. View at Google Scholar
  186. M. R. Loizzo, R. Tundis, F. Menichini, A. M. Saab, and G. A. Statti, “Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells,” Cell Proliferation, vol. 41, pp. 1002–1012, 2008. View at Google Scholar
  187. J. Usta, S. Kreydiyyeh, K. Knio, P. Barnabe, Y. Bou-Moughlabay, and S. Dagher, “Linalool decreases HepG2 viability by inhibiting mitochondrial complexes I and II, increasing reactive oxygen species and decreasing ATP and GSH levels,” Chemico-Biological Interactions, vol. 180, pp. 39–46, 2009. View at Google Scholar
  188. Y. Gu, Z. Tinga, X. Qiua et al., “Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors,” Toxicology, vol. 268, pp. 19–24, 2010. View at Google Scholar
  189. R. Ravizza, M. B. Gariboldi, R. Molteni, and E. Monti, “Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells,” Oncology Reports, vol. 20, pp. 625–630, 2008. View at Google Scholar
  190. H. Maeda, M. Yamazaki, and Y. K. Katagata, “Kuromoji (Lindera umbellata) essential oil-induced apoptosis and differentiation in human leukemia HL-60 cells,” Experimental and Therapeutic Medicine, vol. 3, no. 1, pp. 49–52, 2012. View at Google Scholar
  191. M. Miyashita and Y. Sadzuka, “Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity,” Food and Chemical Toxicology, vol. 53, pp. 174–179, 2013. View at Google Scholar
  192. S. Afoulous, H. Ferhout, E. G. Raoelison et al., “Helichrysum gymnocephalum essential oil: chemical composition and cytotoxic, antimalarial and antioxidant activities, attribution of the activity origin by correlations,” Molecules, vol. 16, pp. 8273–8291, 2011. View at Publisher · View at Google Scholar
  193. C. C. Woo, S. Y. Loo, V. Gee et al., “Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway,” Biochemical Pharmacology, vol. 82, no. 5, pp. 464–475, 2011. View at Publisher · View at Google Scholar