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BioMed Research International
Volume 2015 (2015), Article ID 934207, 14 pages
http://dx.doi.org/10.1155/2015/934207
Review Article

Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

Ning Wang1,2 and Yibin Feng1,2

1School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong
2The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen 518057, China

Received 13 July 2014; Revised 29 September 2014; Accepted 2 October 2014

Academic Editor: Beata Pająk

Copyright © 2015 Ning Wang and Yibin Feng. 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. Glick, S. Barth, and K. F. Macleod, “Autophagy: cellular and molecular mechanisms,” Journal of Pathology, vol. 221, no. 1, pp. 3–12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. R. L. Deter and C. de Duve, “Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes,” The Journal of Cell Biology, vol. 33, no. 2, pp. 437–449, 1967. View at Publisher · View at Google Scholar · View at Scopus
  3. E. Marzetti, S. E. Wohlgemuth, S. D. Anton, R. Bernabei, C. S. Carter, and C. Leeuwenburgh, “Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives,” Clinics in Geriatric Medicine, vol. 25, no. 4, pp. 715–732, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Singh and A. M. Cuervo, “Autophagy in the cellular energetic balance,” Cell Metabolism, vol. 13, no. 5, pp. 495–504, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Denton, S. Nicolson, and S. Kumar, “Cell death by autophagy: facts and apparent artefacts,” Cell Death and Differentiation, vol. 19, no. 1, pp. 87–95, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Tsujimoto and S. Shimizu, “Another way to die: autophagic programmed cell death,” Cell Death and Differentiation, vol. 12, supplement 2, pp. 1528–1534, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Xie, F. Wang, W. L. McKeehan, and L. Liu, “Autophagy enhanced by microtubule- and mitochondrion-associated MAP1S suppresses genome instability and hepatocarcinogenesis,” Cancer Research, vol. 71, no. 24, pp. 7537–7546, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. X. Qu, J. Yu, G. Bhagat et al., “Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1809–1820, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. X. H. Liang, S. Jackson, M. Seaman et al., “Induction of autophagy and inhibition of tumorigenesis by beclin 1,” Nature, vol. 402, no. 6762, pp. 672–676, 1999. View at Publisher · View at Google Scholar · View at Scopus
  10. R. D. Leone and R. K. Amaravadi, “Autophagy: a targetable linchpin of cancer cell metabolism,” Trends in Endocrinology and Metabolism, vol. 24, no. 4, pp. 209–217, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Yang, X. Wang, G. Contino et al., “Pancreatic cancers require autophagy for tumor growth,” Genes & Development, vol. 25, no. 7, pp. 717–729, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. R. K. Amaravadi and C. B. Thompson, “The roles of therapy-induced autophagy and necrosis in cancer treatment,” Clinical Cancer Research, vol. 13, no. 24, pp. 7271–7279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. G. Kallifatidis, D. Hoepfner, T. Jaeg, E. A. Guzmán, and A. E. Wright, “The marine natural product manzamine a targets vacuolar atpases and inhibits autophagy in pancreatic cancer cells,” Marine Drugs, vol. 11, no. 9, pp. 3500–3516, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Lao, G. Wan, Z. Liu et al., “The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation,” Autophagy, vol. 10, no. 5, pp. 736–749, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Chen, Y. Du, M. Qui et al., “Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway,” Oncology Reports, vol. 29, no. 2, pp. 430–436, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Pedro, C. F. Lourenço, H. Cidade, A. Kijjoa, M. Pinto, and M. S. J. Nascimento, “Effects of natural prenylated flavones in the phenotypical ER (+) MCF-7 and ER (-) MDA-MB-231 human breast cancer cells,” Toxicology Letters, vol. 164, no. 1, pp. 24–36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. G. Kaushik, S. Ramalingam, D. Subramaniam et al., “Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells,” The American Journal of Surgery, vol. 204, no. 6, pp. 868–873, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. H. Ko, Y.-J. Kim, E. C. Amor et al., “Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells,” Journal of Cellular Biochemistry, vol. 112, no. 9, pp. 2471–2479, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Dong, S. Yin, C. Jiang et al., “Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-β-D-glucose-induced senescence-like growth arrest in human cancer cells,” Autophagy, vol. 10, no. 2, pp. 296–310, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. B. Y. K. Law, M. Wang, D.-L. Ma et al., “Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis,” Molecular Cancer Therapeutics, vol. 9, no. 3, pp. 718–730, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Guo, G. Wu, J. Bao, W. Hao, J. Lu, and X. Chen, “Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner,” PLoS ONE, vol. 9, no. 2, Article ID e88140, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. D. S. Nkandeu, T. V. Mqoco, M. H. Visagie et al., “In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-β-estradiol analogue in breast adenocarcinoma cells,” Cell Biochemistry and Function, vol. 31, no. 7, pp. 566–574, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. M.-Y. Xu, D. H. Lee, E. J. Joo, K. H. Son, and Y. S. Kim, “Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells,” Food and Chemical Toxicology, vol. 59, pp. 703–708, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Lin, S.-C. Tsai, M. T. Tseng et al., “AKT serine/threonine protein kinase modulates baicalintriggered autophagy in human bladder cancer T24 cells,” International Journal of Oncology, vol. 42, no. 3, pp. 993–1000, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. N. Wang, Y. Feng, M. Zhu et al., “Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism,” Journal of Cellular Biochemistry, vol. 111, no. 6, pp. 1426–1436, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. Q. Hou, X. Tang, H. Liu et al., “Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147,” Cancer Science, vol. 102, no. 7, pp. 1287–1292, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. C.-M. Xie, W. Y. Chan, S. Yu, J. Zhao, and C. H. K. Cheng, “Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation,” Free Radical Biology and Medicine, vol. 51, no. 7, pp. 1365–1375, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. C.-M. Hsu, Y. Tsai, L. Wan, and F.-J. Tsai, “Bufalin induces G2/M phase arrest and triggers autophagy via the TNF, JNK, BECN-1 and ATG8 pathway in human hepatoma cells,” International Journal of Oncology, vol. 43, no. 1, pp. 338–348, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Saiki, Y. Sasazawa, Y. Imamichi et al., “Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition,” Autophagy, vol. 7, no. 2, pp. 176–187, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. H.-W. Lee, K. S. Jang, and K.-H. Chun, “Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy,” BMB Reports, 2014. View at Google Scholar
  31. W.-B. Wang, L.-X. Feng, Q.-X. Yue et al., “Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a natural compound with influence on proteasome, ER stress and Hsp90,” Journal of Cellular Physiology, vol. 227, no. 5, pp. 2196–2206, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. A. M. Hau, J. A. Greenwood, C. V. Löhr et al., “Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells,” PLoS ONE, vol. 8, no. 6, Article ID e65250, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. C.-H. Yan, Z.-Q. Liang, Z.-L. Gu, Y.-P. Yang, P. Reid, and Z.-H. Qin, “Contributions of autophagic and apoptotic mechanisms to CrTX-induced death of K562 cells,” Toxicon, vol. 47, no. 5, pp. 521–530, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. H. Aoki, Y. Takada, S. Kondo, R. Sawaya, B. B. Aggarwal, and Y. Kondo, “Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of akt and extracellular signal-regulated kinase signaling pathways,” Molecular Pharmacology, vol. 72, no. 1, pp. 29–39, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. Y.-L. Jia, J. Li, Z.-H. Qin, and Z.-Q. Liang, “Autophagic and apoptotic mechanisms of curcumin-induced death in K562 cells,” Journal of Asian Natural Products Research, vol. 11, no. 11, pp. 918–928, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. W. Zhuang, L. Long, B. Zheng et al., “Curcumin promotes differentiation of glioma-initiating cells by inducing autophagy,” Cancer Science, vol. 103, no. 4, pp. 684–690, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. B. Li, T. Takeda, K. Tsuiji et al., “Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells,” International Journal of Gynecological Cancer, vol. 23, no. 5, pp. 803–808, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. K. Xiao, J. Jiang, C. Guan et al., “Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells,” Journal of Pharmacological Sciences, vol. 123, no. 2, pp. 102–109, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Rasul, B. Yu, L. Zhong, M. Khan, H. Yang, and T. Ma, “Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy,” Oncology Reports, vol. 27, no. 5, pp. 1481–1487, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Wang, W. Pan, M. Zhu et al., “Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells,” British Journal of Pharmacology, vol. 164, no. 2, pp. 731–742, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. Y.-F. Kuo, Y.-Z. Su, Y.-H. Tseng, S.-Y. Wang, H.-M. Wang, and P. J. Chueh, “Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells,” Free Radical Biology and Medicine, vol. 49, no. 2, pp. 214–226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. W.-S. Xu, T. Li, G.-S. Wu et al., “Effects of furanodiene on 95-d lung cancer cells: apoptosis, autophagy and g1 phase cell cycle arrest,” The American Journal of Chinese Medicine, vol. 42, no. 1, pp. 243–255, 2014. View at Publisher · View at Google Scholar · View at Scopus
  43. W. Mei, C. Dong, C. Hui et al., “Gambogenic acid kills lung cancer cells through aberrant autophagy,” PLoS ONE, vol. 9, no. 1, Article ID e83604, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. K.-H. Chang, M.-D. Yan, C.-J. Yao, P.-C. Lin, and G.-M. Lai, “Honokiol-induced apoptosis and autophagy in glioblastoma multiforme cells,” Oncology Letters, vol. 6, no. 5, pp. 1435–1438, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. M.-Y. Lee, Y.-W. Liu, M.-H. Chen et al., “Indirubin-3′-monoxime promotes autophagic and apoptotic death in JM1 human acute lymphoblastic leukemia cells and K562 human chronic myelogenous leukemia cells,” Oncology Reports, vol. 29, no. 5, pp. 2072–2078, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. J.-L. Chen, C.-J. Chang, J.-Y. Wang et al., “In vitro and in vivo effects of Jia-Wei-Xiao-Yao-San in human breast cancer MCF-7 cells treated with tamoxifen,” Integrative Cancer Therapies, vol. 13, no. 3, pp. 226–239, 2014. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Kim, M. Im, N. H. Yim, T. Kim, and J. Y. Ma, “A novel herbal medicine, KIOM-C, induces autophagic and apoptotic cell death mediated by activation of JNK and reactive oxygen species in HT1080 human fibrosarcoma cells,” PLoS ONE, vol. 9, no. 5, Article ID e98703, 2014. View at Publisher · View at Google Scholar
  48. B. Y. Law, W. K. Chan, S. W. Xu et al., “Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells,” Scientific Reports, vol. 4, article 5510, 2014. View at Publisher · View at Google Scholar
  49. A. Rasul, B. Yu, M. Khan et al., “Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways,” International Journal of Oncology, vol. 40, no. 4, pp. 1153–1161, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. Z. Wang, J. Zhang, Y. Wang et al., “Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases,” Carcinogenesis, vol. 34, no. 1, pp. 128–138, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Poornima, C. F. Weng, and V. V. Padma, “Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells,” Food Chemistry, vol. 141, no. 4, pp. 3598–3605, 2013. View at Publisher · View at Google Scholar · View at Scopus
  52. Q. Deng, X. Yu, L. Xiao et al., “Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway,” Cell Death and Disease, vol. 4, no. 9, article e804, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. G. Yan, S. Lanza-Jacoby, and C. Wang, “Nexrutine inhibits survival and induces G1 cell cycle arrest, which is associated with apoptosis or autophagy depending on the breast cancer cell line,” Nutrition and Cancer, vol. 66, no. 3, pp. 506–516, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. C.-Y. Jin, H. Y. Yu, C. Park et al., “Oleifolioside B-mediated autophagy promotes apoptosis in A549 human non-small cell lung cancer cells,” International Journal of Oncology, vol. 43, no. 6, pp. 1943–1950, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. N.-H. Yim, Y. P. Jung, A. Kim, C. J. Ma, W.-K. Cho, and J. Y. Ma, “Oyaksungisan, a traditional herbal formula, inhibits cell proliferation by induction of autophagy via JNK activation in human colon cancer cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 231874, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. N.-H. Bui-Xuan, P. M.-K. Tang, C.-K. Wong, and K.-P. Fung, “Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231,” Journal of Ethnopharmacology, vol. 131, no. 1, pp. 95–103, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Wang, J.-W. Wang, X. Xiao et al., “Piperlongumine induces autophagy by targeting p38 signaling,” Cell Death and Disease, vol. 4, no. 10, article e824, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. Y.-C. Li, S.-M. He, Z.-X. He et al., “Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells,” Cancer Letters, vol. 344, no. 2, pp. 239–259, 2014. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Wang, Y. Ji, Z. Hu et al., “Riccardin D induces cell death by activation of apoptosis and autophagy in osteosarcoma cells,” Toxicology in Vitro, vol. 27, no. 6, pp. 1928–1936, 2013. View at Publisher · View at Google Scholar · View at Scopus
  60. C. Torricelli, S. Salvadori, G. Valacchi et al., “Alternative pathways of cancer cell death by rottlerin: apoptosis versus autophagy,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 980658, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. V. K. W. Wong, T. Li, B. Y. K. Law et al., “Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells,” Cell Death and Disease, vol. 4, no. 7, article e720, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Kim, N.-H. Yim, and J. Y. Ma, “Samsoeum, a traditional herbal medicine, elicits apoptotic and autophagic cell death by inhibiting Akt/mTOR and activating the JNK pathway in cancer cells,” BMC Complementary and Alternative Medicine, vol. 13, article 233, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. C.-J. Tai, C.-K. Wang, Y.-F. Lin et al., “Aqueous extract of Solanum nigrum leaves induces autophagy and enhances cytotoxicity of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil in human colorectal carcinoma cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 514719, 12 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. W. K. Liu, Y. H. Ling, F. W. K. Cheung, and C.-T. Che, “Stellettin A induces endoplasmic reticulum stress in murine B16 melanoma cells,” Journal of Natural Products, vol. 75, no. 4, pp. 586–590, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. S. M. Yun, J. H. Jung, S. J. Jeong, E. J. Sohn, B. Kim, and S. H. Kim, “Tanshinone IIA induces autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and p70 S6K in KBM-5 leukemia cells,” Phytotherapy Research, vol. 28, no. 3, pp. 458–464, 2014. View at Publisher · View at Google Scholar
  66. W. Qiu, M. Su, F. Xie et al., “Tetrandrine blocks autophagic flux and induces apoptosis via energetic impairment in cancer cells,” Cell Death and Disease, vol. 5, no. 3, Article ID e1123, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. N. Wang, Y. Feng, M. Zhu, F.-M. Siu, K.-M. Ng, and C.-M. Che, “A novel mechanism of XIAP degradation induced by timosaponin AIII in hepatocellular carcinoma,” Biochimica et Biophysica Acta: Molecular Cell Research, vol. 1833, no. 12, pp. 2890–2899, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. A. Thyagarajan, A. Jedinak, H. Nguyen et al., “Triterpenes from ganoderma lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK),” Nutrition and Cancer, vol. 62, no. 5, pp. 630–640, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. C. P. R. Xavier, C. F. Lima, D. F. N. Pedro, J. M. Wilson, K. Kristiansen, and C. Pereira-Wilson, “Ursolic acid induces cell death and modulates autophagy through JNK pathway in apoptosis-resistant colorectal cancer cells,” Journal of Nutritional Biochemistry, vol. 24, no. 4, pp. 706–712, 2013. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Kundu, T. H. Kim, J. H. Yoon et al., “Viriditoxin regulates apoptosis and autophagy via mitotic catastrophe and microtubule formation in human prostate cancer cells,” International Journal of Oncology, pp. 2331–2340, 2014. View at Publisher · View at Google Scholar
  71. J. Zhou, H. Hu, J. Long et al., “Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway,” Anti-Cancer Drugs, vol. 24, no. 9, pp. 928–936, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Meschini, M. Condello, A. Calcabrini et al., “The plant alkaloid voacamine induces apoptosis-independent autophagic cell death on both sensitive and multidrug resistant human osteosarcoma cells,” Autophagy, vol. 4, no. 8, pp. 1020–1033, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Huo, F. Qin, X. Cai et al., “Chinese medicine formula “weikang Keli” induces autophagic cell death on human gastric cancer cell line SGC-7901,” Phytomedicine, vol. 20, no. 2, pp. 159–165, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. J.-M. Eom, M.-J. Seo, J.-Y. Baek et al., “Alpha-eleostearic acid induces autophagy-dependent cell death through targeting AKT/mTOR and ERK1/2 signal together with the generation of reactive oxygen species,” Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 903–908, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. C. H. Jung, H. Kim, J. Ahn et al., “Anthricin isolated from Anthriscus sylvestris (L.) Hoffm. inhibits the growth of breast cancer cells by inhibiting Akt/mTOR signaling, and its apoptotic effects are enhanced by autophagy inhibition,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 385219, 9 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. D.-M. Zhang, J.-S. Liu, L.-J. Deng et al., “Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway,” Carcinogenesis, vol. 34, no. 6, pp. 1331–1342, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Liu, Y. Zhang, J. Qu et al., “β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis,” BMC Cancer, vol. 11, article 183, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Liu, X.-J. Hu, B. Jin, X.-J. Qu, K.-Z. Hou, and Y.-P. Liu, “β-elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells,” Journal of Pharmacy and Pharmacology, vol. 64, no. 1, pp. 146–153, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. H. Zhan, J. Liu, X. J. Qu et al., “β-Elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of mAPK/ERK and PI3K/Akt/mtor signalling pathways,” Asian Pacific Journal of Cancer Prevention, vol. 13, no. 6, pp. 2739–2744, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. S.-C. Tsai, J.-S. Yang, S.-F. Peng et al., “Bufalin increases sensitivity to AKT/mTOR-induced autophagic cell death in SK-HEP-1 human hepatocellular carcinoma cells,” International Journal of Oncology, vol. 41, no. 4, pp. 1431–1442, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Shen, Y. Zhang, Z. Wang, R. Liu, and X. Gong, “Bufalin induces the interplay between apoptosis and autophagy in glioma cells through endoplasmic reticulum stress,” International Journal of Biological Sciences, vol. 10, no. 2, pp. 212–224, 2014. View at Publisher · View at Google Scholar · View at Scopus
  82. G. Yuan, S.-F. Yan, H. Xue, P. Zhang, J.-T. Sun, and G. Li, “Cucurbitacin i induces protective autophagy in glioblastoma in vitro and in vivo,” The Journal of Biological Chemistry, vol. 289, no. 15, pp. 10607–10619, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. M.-J. Hsieh, S.-F. Yang, Y.-S. Hsieh, T.-Y. Chen, and H.-L. Chiou, “Autophagy inhibition enhances apoptosis induced by dioscin in Huh7 cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 134512, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. R. T. Williams, A. L. Yu, M. B. Diccianni, E. A. Theodorakis, and A. Batova, “Renal cancer-selective Englerin A induces multiple mechanisms of cell death and autophagy,” Journal of Experimental and Clinical Cancer Research, vol. 32, no. 1, article 57, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. P. Gao, C. Bauvy, S. Souquère et al., “The Bcl-2 homology domain 3 mimetic gossypol induces both beclin 1-dependent and beclin 1-independent cytoprotective autophagy in cancer cells,” The Journal of Biological Chemistry, vol. 285, no. 33, pp. 25570–25581, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Zhao, C.-M. Ma, C.-X. Liu et al., “Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells,” International Journal of Molecular Medicine, vol. 30, no. 4, pp. 939–944, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Zhang, H. Wang, J. Zhu, J. Xu, and K. Ding, “Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6K and ERK signaling pathways,” Biochemical and Biophysical Research Communications, vol. 450, pp. 247–254, 2014. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Lu, W. Wang, Y. Jia, X. Liu, Z. Tong, and B. Li, “Inhibition of AMPK/autophagy potentiates parthenolide-induced apoptosis in human breast cancer cells,” Journal of Cellular Biochemistry, vol. 115, no. 8, pp. 1458–1466, 2014. View at Publisher · View at Google Scholar
  89. H. He, L.-H. Zang, Y.-S. Feng et al., “Physalin A induces apoptosis via p53-Noxa-mediated ROS generation, and autophagy plays a protective role against apoptosis through p38-NF-κB survival pathway in A375-S2 cells,” Journal of Ethnopharmacology, vol. 148, no. 2, pp. 544–555, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Wang, T. Yu, C. Zhu et al., “Resveratrol triggers protective autophagy through the ceramide/Akt/mTOR pathway in melanoma B16 cells,” Nutrition and Cancer, vol. 66, no. 3, pp. 435–440, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Yamamoto, S. O. Suzuki, and M. Himeno, “Resveratrol-induced autophagy in human U373 glioma cells,” Oncology Letters, vol. 1, no. 3, pp. 489–493, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. E. C. Filippi-Chiela, E. S. Villodre, L. L. Zamin, and G. Lenz, “Autophagy interplay with apoptosis and cell cycle regulation in the growth inhibiting effect of resveratrol in glioma cells,” PLoS ONE, vol. 6, no. 6, Article ID e20849, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. R. Roy, D. Kumar, B. Chakraborty, C. Chowdhury, and P. Das, “Apoptotic and autophagic effects of Sesbania grandiflora flowers in human leukemic cells,” PLoS ONE, vol. 8, no. 8, Article ID e71672, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. S.-E. Chow, Y.-W. Chen, C.-A. Liang, Y.-K. Huang, and J.-S. Wang, “Wogonin induces cross-regulation between autophagy and apoptosis via a variety of Akt pathway in human nasopharyngeal carcinoma cells,” Journal of Cellular Biochemistry, vol. 113, no. 11, pp. 3476–3485, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Wang, W. Zheng, X. Bian et al., “Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells,” Toxicology Letters, vol. 226, no. 2, pp. 182–191, 2014. View at Publisher · View at Google Scholar · View at Scopus
  96. L. E. Broker, F. A. E. Kruyt, and G. Giaccone, “Cell death independent of caspases: a review,” Clinical Cancer Research, vol. 11, no. 9, pp. 3155–3162, 2005. View at Publisher · View at Google Scholar · View at Scopus
  97. G.-Z. Zhou, S.-L. Xu, G.-C. Sun, and X.-B. Chen, “Novel curcumin analogue IHCH exhibits potent anti-proliferative effects by inducing autophagy in A549 lung cancer cells,” Molecular Medicine Reports, vol. 10, no. 1, pp. 441–446, 2014. View at Publisher · View at Google Scholar · View at Scopus
  98. D. Maskey, S. Yousefi, I. Schmid et al., “ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy,” Nature Communications, vol. 4, article 2130, 2013. View at Publisher · View at Google Scholar · View at Scopus
  99. Q. Miao, L.-L. Bi, X. Li et al., “Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 Cells: roles of apoptosis and autophagy,” International Journal of Molecular Sciences, vol. 14, no. 1, pp. 1370–1382, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. V. Rogov, V. Dötsch, T. Johansen, and V. Kirkin, “Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy,” Molecular Cell, vol. 53, no. 2, pp. 167–178, 2014. View at Publisher · View at Google Scholar · View at Scopus
  101. R. Kang, H. J. Zeh, M. T. Lotze, and D. Tang, “The Beclin 1 network regulates autophagy and apoptosis,” Cell Death and Differentiation, vol. 18, no. 4, pp. 571–580, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Kwatra, D. Subramaniam, P. Ramamoorthy et al., “Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting energy homeostasis and autophagy,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 702869, 14 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. C. Porta, C. Paglino, and A. Mosca, “Targeting PI3K/Akt/mTOR signaling in cancer,” Frontiers in Oncology, vol. 4, article 64, 2014. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Rikiishi, “Novel insights into the interplay between apoptosis and autophagy,” International Journal of Cell Biology, vol. 2012, Article ID 317645, 14 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. H. Maes, N. Rubio, A. D. Garg, and P. Agostinis, “Autophagy: shaping the tumor microenvironment and therapeutic response,” Trends in Molecular Medicine, vol. 19, no. 7, pp. 428–446, 2013. View at Publisher · View at Google Scholar · View at Scopus
  106. J. L. Liu, F. F. Chen, J. Lung et al., “Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma,” British Journal of Cancer, vol. 111, no. 5, pp. 944–954, 2014. View at Publisher · View at Google Scholar
  107. D. J. Klionsky, F. C. Abdalla, H. Abeliovich et al., “Guidelines for the use and interpretation of assays for monitoring autophagy,” Autophagy, vol. 8, no. 4, pp. 445–544, 2012. View at Google Scholar
  108. E. Schmukler, Y. Kloog, and R. Pinkas-Kramarski, “Ras and autophagy in cancer development and therapy,” Oncotarget, vol. 5, no. 3, pp. 577–586, 2014. View at Google Scholar · View at Scopus
  109. C. Kantara, M. O'Connell, S. Sarkar, S. Moya, R. Ullrich, and P. Singh, “Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA,” Cancer Research, vol. 74, no. 9, pp. 2487–2498, 2014. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Fulda, “Tumor resistance to apoptosis,” International Journal of Cancer, vol. 124, no. 3, pp. 511–515, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. F. Hu, J. Han, B. Zhai et al., “Blocking autophagy enhances the apoptosis effect of bufalin on human hepatocellular carcinoma cells through endoplasmic reticulum stress and JNK activation,” Apoptosis, vol. 19, no. 1, pp. 210–223, 2014. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Mathew, C. M. Karp, B. Beaudoin et al., “Autophagy suppresses tumorigenesis through elimination of p62,” Cell, vol. 137, no. 6, pp. 1062–1075, 2009. View at Publisher · View at Google Scholar
  113. Z. J. Yang, C. E. Chee, S. Huang, and F. A. Sinicrope, “The role of autophagy in cancer: therapeutic implications,” Molecular Cancer Therapeutics, vol. 10, no. 9, pp. 1533–1541, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. G. Mariño, M. Niso-Santano, E. H. Baehrecke, and G. Kroemer, “Self-consumption: the interplay of autophagy and apoptosis,” Nature Reviews Molecular Cell Biology, vol. 15, no. 2, pp. 81–94, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. C. He and D. J. Klionsky, “Analyzing autophagy in zebrafish,” Autophagy, vol. 6, no. 5, pp. 642–644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. F. Tian, N. Morimoto, W. Liu et al., “In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis,” Autophagy, vol. 7, no. 9, pp. 985–992, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. F. Tian, K. Deguchi, T. Yamashita et al., “In vivo imaging of autophagy in a mouse stroke model,” Autophagy, vol. 6, no. 8, pp. 1107–1114, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. K. Man, K. T. P. Ng, A. Xu et al., “Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling,” Clinical Cancer Research, vol. 16, no. 3, pp. 967–977, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. T. Farkas, M. Høyer-Hansen, and M. Jäättelä, “Identification of novel autophagy regulators by a luciferase-based assay for the kinetics of autophagic flux,” Autophagy, vol. 5, no. 7, pp. 1018–1025, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. P.-L. Peng, W.-H. Kuo, H.-C. Tseng, and F.-P. Chou, “Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death,” International Journal of Radiation Oncology Biology Physics, vol. 70, no. 2, pp. 529–542, 2008. View at Publisher · View at Google Scholar · View at Scopus
  121. D. Ma, P. Tremblay, K. Mahngar, J. Collins, T. Hudlicky, and S. Pandey, “Selective cytotoxicity against human osteosarcoma cells by a novel synthetic C-1 analogue of 7-deoxypancratistatin is potentiated by curcumin,” PLoS ONE, vol. 6, no. 12, Article ID e28780, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. E. J. Wu, D. J. Goussetis, E. Beauchamp et al., “Resveratrol enhances the suppressive effects of arsenic trioxide on primitive leukemic progenitors,” Cancer Biology and Therapy, vol. 15, no. 4, pp. 473–478, 2014. View at Publisher · View at Google Scholar · View at Scopus
  123. A. De, C. Papasian, S. Hentges, S. Banerjee, I. Haque, and S. K. Banerjee, “Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors,” PLoS ONE, vol. 8, no. 8, Article ID e72748, 2013. View at Publisher · View at Google Scholar · View at Scopus
  124. Y.-Y. Chiang, S.-L. Wang, C.-L. Yang et al., “Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects,” International Journal of Molecular Medicine, vol. 32, no. 3, pp. 577–584, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. Z. Meng, P. Yang, Y. Shen et al., “Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer,” Cancer, vol. 115, no. 22, pp. 5309–5318, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. D. J. Boocock, G. E. S. Faust, K. R. Patel et al., “Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent,” Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 6, pp. 1246–1252, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. H.-H. S. Chow, L. L. Garland, C.-H. Hsu et al., “Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study,” Cancer Prevention Research, vol. 3, no. 9, pp. 1168–1175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. K. R. Patel, V. A. Brown, D. J. L. Jones et al., “Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients,” Cancer Research, vol. 70, no. 19, pp. 7392–7399, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. R. Popat, T. Plesner, F. Davies et al., “A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma,” The British Journal of Haematology, vol. 160, no. 5, pp. 714–717, 2013. View at Publisher · View at Google Scholar · View at Scopus