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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 247597, 18 pages
http://dx.doi.org/10.1155/2012/247597
Review Article

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

1Department of Biomedical Science, Faculty of Basic and Health Science, Santiago de Cali University, Pampalinda Campus, Cali, Colombia
2Division of Molecular and Gene Therapies, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast Campus, Southport, QLD 4222, Australia

Received 1 August 2011; Accepted 29 August 2011

Academic Editor: Masa-Aki Shibata

Copyright © 2012 Maria P. Crespo-Ortiz and Ming Q. Wei. 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.

Citations to this Article [97 citations]

The following is the list of published articles that have cited the current article.

  • Ying Li, “Qinghaosu (artemisinin): Chemistry and pharmacology,” Acta Pharmacologica Sinica, vol. 33, no. 9, pp. 1141–1146, 2012. View at Publisher · View at Google Scholar
  • Nicholas M Njuguna, Dennis S B Ongarora, and Kelly Chibale, “Artemisinin derivatives: a patent review (2006 – present),” Expert Opinion on Therapeutic Patents, vol. 22, no. 10, pp. 1179–1203, 2012. View at Publisher · View at Google Scholar
  • Fei Zhao, Han Wang, Patricilia Kunda, Xuemei Chen, Qiu-Ling Liu, and Tao Liu, “Artesunate exerts specific cytotoxicity in retinoblastoma cells via CD71,” Oncology Reports, vol. 30, no. 3, pp. 1473–1482, 2013. View at Publisher · View at Google Scholar
  • A. Flobinus, N. Taudon, M. Desbordes, B. Labrosse, F. Simon, M.-C. Mazeron, and N. Schnepf, “Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives,” Journal of Antimicrobial Chemotherapy, 2013. View at Publisher · View at Google Scholar
  • Tamara Wriessnegger, and Harald Pichler, “Yeast metabolic engineering – Targeting sterol metabolism and terpenoid formation,” Progress in Lipid Research, vol. 52, no. 3, pp. 277–293, 2013. View at Publisher · View at Google Scholar
  • Bryan T. Mott, Ran He, Xiaochun Chen, Jennifer M. Fox, Curt I. Civin, Ravit Arav-Boger, and Gary H. Posner, “Artemisinin-derived dimer phosphate esters as potent anti-cytomegalovirus (anti-CMV) and anti-cancer agents: A structure–activity study,” Bioorganic & Medicinal Chemistry, vol. 21, no. 13, pp. 3702–3707, 2013. View at Publisher · View at Google Scholar
  • Kirsten Vandercruyssen, Matthias D'Hondt, Valentijn Vergote, Herwig Jansen, Christian Burvenich, and Bart De Spiegeleer, “LC-UV/MS quality analytics of paediatric artemether formulations,” Journal of Pharmaceutical Analysis, 2013. View at Publisher · View at Google Scholar
  • Jun Lee, Peiqiang Shen, Guobing Zhang, Xiuhua Wu, and Xingguo Zhang, “Dihydroartemisinin inhibits the Bcr/Abl oncogene at the mRNA level in chronic myeloid leukemia sensitive or resistant to imatinib,” Biomedicine & Pharmacotherapy, vol. 67, no. 2, pp. 157–163, 2013. View at Publisher · View at Google Scholar
  • Jian-Quan Shi, Chu-Chu Zhang, Xiu-Lan Sun, Xin-Xin Cheng, Jiang-Bo Wang, Ying-Dong Zhang, Jun Xu, and Hai-Qiang Zou, “Antimalarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/PS1dE9 Transgenic Mice via Inhibition of Nuclear Factor-κB and NLRP3 Inflammasome Activation,” CNS Neuroscience & Therapeutics, vol. 19, no. 4, pp. 262–268, 2013. View at Publisher · View at Google Scholar
  • Rob Hooft van Huijsduijnen, R. Kiplin Guy, Kelly Chibale, Richard K. Haynes, Ingmar Peitz, Gerhard Kelter, Margaret A. Phillips, Jonathan L. Vennerstrom, and Yongyuth Yuthavong, “Anticancer Properties of Distinct Antimalarial Drug Classes,” Plos One, vol. 8, no. 12, 2013. View at Publisher · View at Google Scholar
  • Li-Peng Qiu, Liang Chen, and Ke-Ping Chen, “Antihepatitis B therapy: a review of current medications and novel small molecule inhibitors,” Fundamental & Clinical Pharmacology, 2013. View at Publisher · View at Google Scholar
  • Bianca C. Pérez, Iva Fernandes, Nuno Mateus, Cátia Teixeira, and Paula Gomes, “Recycling antimalarial leads for cancer: antiproliferative properties of N-cinnamoyl chloroquine analogues,” Bioorganic & Medicinal Chemistry Letters, 2013. View at Publisher · View at Google Scholar
  • Tatiana Küster, Nadja Kriegel, Britta Stadelmann, Xiaofang Wang, Yuxiang Dong, Jonathan L. Vennerstrom, Jennifer Keiser, and Andrew Hemphill, “Amino ozonides exhibit in vitro activity against Echinococcus multilocularis metacestodes,” International Journal of Antimicrobial Agents, 2013. View at Publisher · View at Google Scholar
  • Li-Peng Qiu, and Ke-Ping Chen, “Anti-HBV agents derived from botanical origin,” Fitoterapia, vol. 84, pp. 140–157, 2013. View at Publisher · View at Google Scholar
  • Valeria V. Costantino, Luis A. Lopez, Sabrina F. Mansilla, Juliana Speroni, Celina Amaya, Darío Cuello-Carrión, Daniel R. Ciocca, Horacio A. Priestap, Manuel A. Barbieri, and Vanesa Gottifredi, “The Sesquiterpene Lactone Dehydroleucodine Triggers Senescence and Apoptosis in Association with Accumulation of DNA Damage Markers,” PLoS ONE, vol. 8, no. 1, 2013. View at Publisher · View at Google Scholar
  • Soek Sin Teh, Gwendoline Cheng Lian Ee, Siau Hui Mah, Yoke Keong Yong, Yang Mooi Lim, Mawardi Rahmani, and Zuraini Ahmad, “In Vitro Cytotoxic, Antioxidant, and Antimicrobial Activities of Mesua beccariana (Baill.) Kosterm., Mesua ferrea Linn., and Mesua congestiflora Extracts,” BioMed Research International, vol. 2013, pp. 1–9, 2013. View at Publisher · View at Google Scholar
  • Rui-jian Jiang, Yu-lin Zhao, Yun-jian Chen, Dan Xiao, Fen Wang, Bin Han, Jian Yang, Xia-li Liao, Li-Juan Yang, Chuan-zhu Gao, and Bo Yang, “Synthesis, characterization and in vitro evaluation of artesunate-β-cyclodextrin conjugates as novel anti-cancer prodrugs,” Carbohydrate Research, 2014. View at Publisher · View at Google Scholar
  • Donna M. Raditic, and Joseph W. Bartges, “Evidence-based Integrative Medicine in Clinical Veterinary Oncology,” Veterinary Clinics of North America: Small Animal Practice, vol. 44, no. 5, pp. 831–853, 2014. View at Publisher · View at Google Scholar
  • Shunqin Zhu, Wanhong Liu, Xiaoxue Ke, Jifu Li, Renjian Hu, Hongjuan Cui, and Guanbin Song, “Artemisinin reduces cell proliferation and induces apoptosis in neuroblastoma,” Oncology Reports, vol. 32, no. 3, pp. 1094–1100, 2014. View at Publisher · View at Google Scholar
  • Yves-Paul Vandewynckel, Debby Laukens, Anja Geerts, Chris Vanhove, Benedicte Descamps, Isabelle Colle, Lindsey Devisscher, Eliene Bogaerts, Annelies Paridaens, Xavier Verhelst, Christophe Van Steenkiste, Louis Libbrecht, Bart N. Lambrecht, Sophie Janssens, and Hans Van Vlierberghe, “Therapeutic effects of artesunate in hepatocellular carcinoma,” European Journal of Gastroenterology & Hepatology, vol. 26, no. 8, pp. 861–870, 2014. View at Publisher · View at Google Scholar
  • Muzamil Yaqub Want, Mohammad Islamuddin, Garima Chauhan, Anjan Kumar Dasgupta, Asoke Prasun Chattopadhyay, and Farhat Afrin, “A new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies,” Journal of Colloid and Interface Science, 2014. View at Publisher · View at Google Scholar
  • Sourajit Soumyaranjan Das, Gargi Gouranga Nanda, and Debasmita Pankaj Alone, “ Artemisinin and Curcumin inhibit Drosophila brain tumor, prolong life span, and restore locomotor activity ,” IUBMB Life, 2014. View at Publisher · View at Google Scholar
  • Ji-ye Yin, He-mei Wang, Quan-jun Wang, Yan-sheng Dong, Gang Han, Yong-biao Guan, Ke-yong Zhao, Wen-sheng Qu, Ye Yuan, Xiao-xin Gao, Shu-fang Jing, and Ri-gao Ding, “Subchronic Toxicological Study of Two Artemisinin Derivatives in Dogs,” Plos One, vol. 9, no. 4, 2014. View at Publisher · View at Google Scholar
  • Julie Lotharius, Francisco Javier Gamo-Benito, Inigo Angulo-Barturen, Julie Clark, Michele Connelly, Santiago Ferrer-Bazaga, Tanya Parkinson, Pavithra Viswanath, Balachandra Bandodkar, Nikhil Rautela, Sowmya Bharath, Sandra Duffy, Vicky M. Avery, R. Kiplin Guy, and Timothy Wells, “Repositioning: the fast track to new anti-malarial medicines?,” Malaria Journal, vol. 13, 2014. View at Publisher · View at Google Scholar
  • Yan Yang, Xiaomin Zhang, Xiaofen Wang, Xiaomei Zhao, Tianrui Ren, Feng Wang, and Bo Yu, “Enhanced delivery of artemisinin and its analogues to cancer cells by their adducts with human serum transferrin,” International Journal of Pharmaceutics, 2014. View at Publisher · View at Google Scholar
  • Juan P. Joubert, Frans J. Smit, Lissinda du Plessis, Peter J. Smith, and David D. N’Da, “Synthesis and in vitro biological evaluation of aminoacridines and artemisinin-acridine hybrids,” European Journal of Pharmaceutical Sciences, 2014. View at Publisher · View at Google Scholar
  • Fengyun Dong, Xia Zhou, Changsheng Li, Suhua Yan, Xianming Deng, Zhiqun Cao, Liqun Li, Bo Tang, Thaddeus D Allen, and Ju Liu, “Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis,” Cancer Biology & Therapy, vol. 15, no. 11, pp. 1479–1488, 2014. View at Publisher · View at Google Scholar
  • Ling Guo, Fengyun Dong, Yinglong Hou, Weidong Cai, Xia Zhou, Al-Ling Huang, Min Yang, Thaddeus D. Allen, and Ju Liu, “Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independen,” Experimental And Therapeutic Medicine, vol. 8, no. 6, pp. 1707–1712, 2014. View at Publisher · View at Google Scholar
  • Paul Chidoka Chikezie, “Comparative Erythrocyte Glutathione S-Transferase Activity Profile of Non-Malarious Guinea Pigs (Cavia tschudii) Administered Pyrimethamine/Sulfadoxine and Artemether/Lumefantrine Combination Therapies,” Thrita, vol. 3, no. 4, 2014. View at Publisher · View at Google Scholar
  • Sushma Gupta, and Renu Chadha, “Evaluation of compatibility among artemether, pyrimethamine and sulphadoxine using analytical and isothermal calorimetry techniques,” Journal of Thermal Analysis and Calorimetry, 2014. View at Publisher · View at Google Scholar
  • Huijuan Zhang, Lin Hou, Xiaojing Jiao, Yandan Ji, Xiali Zhu, and Zhenzhong Zhang, “Transferrin-mediated fullerenes nanoparticles as Fe2+-dependent drug vehicles for synergistic anti-tumor efficacy,” Biomaterials, 2014. View at Publisher · View at Google Scholar
  • Christoph Reiter, Aysun Çapci Karagöz, Tony Fröhlich, Volker Klein, Maen Zeino, Katrin Viertel, Jana Held, Benjamin Mordmüller, Safiye Emirdağ Öztürk, Hüseyin Anil, Thomas Efferth, and Svetlana B. Tsogoeva, “Synthesis and study of cytotoxic activity of 1,2,4-trioxane- and egonol-derived hybrid molecules against Plasmodium falciparum and multidrug-resistant human leukemia cells,” European Journal of Medicinal Chemistry, 2014. View at Publisher · View at Google Scholar
  • Suganthi Appalasamy, Kiah Yann Lo, Song Jin Ch'ng, Ku Nornadia, Ahmad Sofiman Othman, and Lai-Keng Chan, “Antimicrobial Activity of Artemisinin and Precursor Derived from In Vitro Plantlets of Artemisia annua L.,” BioMed Research International, vol. 2014, pp. 1–6, 2014. View at Publisher · View at Google Scholar
  • Xuanbin Wang, Yibin Feng, Ning Wang, Fan Cheung, Hor Yue Tan, Sen Zhong, Charlie Li, and Seiichi Kobayashi, “Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy,” BioMed Research International, vol. 2014, pp. 1–14, 2014. View at Publisher · View at Google Scholar
  • Ji-Ye Yin, He-Mei Wang, and Ri-Gao Ding, “Artemisinin and its derivatives: Progress in toxicology,” Chinese Journal of Pharmacology and Toxicology, vol. 28, no. 2, pp. 309–314, 2014. View at Publisher · View at Google Scholar
  • YuLiang Wang, ZeJian Wang, Ming Yin, and HaiLiang Xin, “Study on general pharmacology and preliminary toxicity of the compound of artesunate and ursolic acid,” Pharmaceutical Care and Research, vol. 14, no. 3, pp. 192–194, 2014. View at Publisher · View at Google Scholar
  • Paul Chidoka Chikezie, “Comparative erythrocyte glutathione S-transferase activity profile of non-malarious Guinea pigs (Cavia tschudii) administered with pyrimethamine/sulphadoxine and artemether/lumefantrine combination therapies,” Asian Journal of Biochemistry, vol. 9, no. 4, pp. 203–212, 2014. View at Publisher · View at Google Scholar
  • Anupma Dwivedi, Anisha Mazumder, Lissinda du Plessis, Jan L. du Preez, Richard K. Haynes, and Jeanetta du Plessis, “In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells,” Nanomedicine: Nanotechnology, Biology and Medicine, 2015. View at Publisher · View at Google Scholar
  • Guiqi Qin, ChuBiao Zhao, Lili Zhang, Hongyu Liu, Yingyao Quan, Liuying Chai, Shengnan Wu, Xiaoping Wang, and Tongsheng Chen, “Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells,” Apoptosis, vol. 20, no. 8, pp. 1072–1086, 2015. View at Publisher · View at Google Scholar
  • Xing Yan, Yang Yu, Peng Ji, Hui He, and Chunhua Qiao, “Antitumor Activity of Endoperoxide-Iron Chelator Conjugates―Design, Synthesis and Biological Evaluation,” European Journal of Medicinal Chemistry, 2015. View at Publisher · View at Google Scholar
  • J. F. O'Neill, R. C. Johnston, L. Halferty, R. E. B. Hanna, G. P. Brennan, and I. Fairweather, “A comparative study on the impact of two artemisinin derivatives, artemether and artesunate, on the female reproductive system of Fasciola hepatica,” Veterinary Parasitology, vol. 211, no. 3-4, pp. 182–194, 2015. View at Publisher · View at Google Scholar
  • Guiqi Qin, Liping Wu, Hongyu Liu, Yilin pang, Chubiao Zhao, Shengnan Wu, Xiaoping Wang, and Tongsheng Chen, “Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells,” Experimental Cell Research, 2015. View at Publisher · View at Google Scholar
  • Sara Beccafico, Giulio Morozzi, Maria Cristina Marchetti, Carlo Riccardi, Angelo Sidoni, Rosario Donato, and Guglielmo Sorci, “ Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells ,” Carcinogenesis, pp. bgv098, 2015. View at Publisher · View at Google Scholar
  • Fengyun Dong, Hu Tian, Suhua Yan, Liqun Li, Xiaofeng Dong, Fuhai Wang, Jie Li, Changsheng Li, Zhiqun Cao, Xiaochun Liu, and Ju Liu, “Dihydroartemisinin inhibits endothelial cell proliferation through the suppression of the ERK signaling pathway,” International Journal Of Molecular Medicine, vol. 35, no. 5, pp. 1381–1387, 2015. View at Publisher · View at Google Scholar
  • Chanakya Nath Kundu, Sarita Das, Anmada Nayak, Shakti Ranjan Satapathy, Dipon Das, and Sumit Siddharth, “Anti-malarials are anti-cancers and vice versa- one arrow two sparrows,” Acta Tropica, 2015. View at Publisher · View at Google Scholar
  • Nguyen Phuong Thao, Bui Thi Thuy Luyen, Chau Ngoc Diep, Bui Huu Tai, Eun Ji Kim, Hee Kyoung Kang, Sang Hyun Lee, Hae Dong Jang, Nguyen The Cuong, Nguyen Van Thanh, Nguyen Xuan Cuong, Nguyen Hoai Nam, Chau Van Minh, and Young Ho Kim, “In vitro evaluation of the antioxidant and cytotoxic activities of constituents of the mangrove Lumnitzera racemosa Willd.,” Archives Of Pharmacal Research, vol. 38, no. 4, pp. 446–455, 2015. View at Publisher · View at Google Scholar
  • Christoph Reiter, Tony Fröhlich, Maen Zeino, Manfred Marschall, Hanife Bahsi, Maria Leidenberger, Oliver Friedrich, Barbara Kappes, Frank Hampel, Thomas Efferth, and Svetlana B. Tsogoeva, “New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane-ferrocene hybrids,” European Journal of Medicinal Chemistry, 2015. View at Publisher · View at Google Scholar
  • J.F. O'Neill, R.C. Johnston, L. Halferty, G.P. Brennan, and I. Fairweather, “Ultrastructural changes in the tegument and gut of adult fasciola hepatica following in vivo treatment with artesunate.,” Experimental Parasitology, 2015. View at Publisher · View at Google Scholar
  • Muzamil Yaqub Want, Mohammad Islamuddin, Garima Chouhan, Hani A. Ozbak, Hassan A. Hemeg, Anjan Kumar Dasgupta, Asoke Prasun Chattopadhyay, and Farhat Afrin, “Therapeutic efficacy of artemisinin-loaded nanoparticles in experimental visceral leishmaniasis,” Colloids and Surfaces B: Biointerfaces, 2015. View at Publisher · View at Google Scholar
  • Hexin Tan, Ling Xiao, Shouhong Gao, Qing Li, Junfeng Chen, Ying Xiao, Qian Ji, Ruibing Chen, Wansheng Chen, and Lei Zhang, “,” Molecular Plant, 2015. View at Publisher · View at Google Scholar
  • Shazia Khan, Athar Ali, Shahzad Ahmad, and Malik Zainul Abdin, “ Affordable and rapid HPTLC method for the simultaneous analysis of artemisinin and its metabolite artemisinic acid in Artemisia annua L. ,” Biomedical Chromatography, 2015. View at Publisher · View at Google Scholar
  • Maria Bräutigam, Nicole Teusch, Tobias Schenk, Miriam Sheikh, Rocky Z. Aricioglu, Swantje H. Borowski, Jörg-Martin Neudörfl, Ulrich Baumann, Axel G. Griesbeck, and Markus Pietsch, “Selective Inhibitors of Glutathione Transferase P1 with Trioxane Structure as Anticancer Agents,” ChemMedChem, 2015. View at Publisher · View at Google Scholar
  • Tuan Hiep Tran, Tuan Duc Nguyen, Bijay Kumar Poudel, Hanh Thuy Nguyen, Jong Oh Kim, Chul Soon Yong, and Chien Ngoc Nguyen, “Development and Evaluation of Artesunate-Loaded Chitosan-Coated Lipid Nanocapsule as a Potential Drug Delivery System Against Breast Cancer,” Aaps Pharmscitech, vol. 16, no. 6, pp. 1307–1316, 2015. View at Publisher · View at Google Scholar
  • Tengfei Huang, Cuiping Li, Xingzhi Sun, Zhenfu Zhu, Yun Fu, Youxun Liu, Yanbin Yuan, Shaoshan Li, and Changzheng Li, “The antitumor mechanism of di-2-pyridylketone 2-pyridine carboxylic acid hydrazone and its copper complex in ROS generation and topoisomerase inhibiti,” International Journal Of Oncology, vol. 47, no. 5, pp. 1854–1862, 2015. View at Publisher · View at Google Scholar
  • Zhi-Qiang Yan, Dan-Dan Wang, Lan Ding, Hai-Yan Cui, Hui Jin, Xiao-Yan Yang, Jian-She Yang, and Bo Qin, “Mechanism of artemisinin phytotoxicity action: Induction of reactive oxygen species and cell death in lettuce seedlings,” Plant Physiology and Biochemistry, 2015. View at Publisher · View at Google Scholar
  • Bianca Ivanescu, Anca Miron, and Andreia Corciova, “ Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis ,” Journal of Analytical Methods in Chemistry, vol. 2015, pp. 1–21, 2015. View at Publisher · View at Google Scholar
  • Hoang Nhan Ho, Tuan Hiep Tran, Trong Bien Tran, Chul Soon Yong, and Chien Ngoc Nguyen, “Optimization and Characterization of Artesunate-Loaded Chitosan-Decorated Poly(D,L-lactide-co-glycolide) Acid Nanoparticles,” Journal of Nanomaterials, vol. 2015, pp. 1–12, 2015. View at Publisher · View at Google Scholar
  • Michael A. Corsello, and Neil K. Garg, “Synthetic chemistry fuels interdisciplinary approaches to the production of artemisinin,” Nat. Prod. Rep., vol. 32, no. 3, pp. 359–366, 2015. View at Publisher · View at Google Scholar
  • Hai-Jun Chen, Xiu-Rong Huang, Xiao-Bin Zhou, Bi-Yuan Zheng, and Jian-Dong Huang, “Potential sonodynamic anticancer activities of artemether and liposome-encapsulated artemether,” Chem. Commun., vol. 51, no. 22, pp. 4681–4684, 2015. View at Publisher · View at Google Scholar
  • Da Eun Jeong, Han Yong Choi, Hye Won Lee, Hye Jin Song, Sharon Lim, Se Jeong Lee, Joung Eun Lim, Do-Hyun Nam, Kyeung Min Joo, Byong Chang Jeong, and Seong Soo Jeon, “Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis,” Oncotarget, vol. 6, no. 32, pp. 33046–33064, 2015. View at Publisher · View at Google Scholar
  • Jennifer M. Fox, Gary H. Posner, Curt I. Civin, Xiaochun Chen, James R. Moynihan, Bryan T. Mott, Jennifer R. Mazzone, Nicole M. Anders, Patrick A. Brown, Michelle A. Rudek, Jun O. Liu, and Ravit Arav-Boger, “Artemisinin-derived dimer ART-838 potently inhibited human acute leukemias, persisted in vivo, and synergized with antileukemic drugs,” Oncotarget, vol. 7, no. 6, pp. 7268–7279, 2015. View at Publisher · View at Google Scholar
  • Dejan M. Opsenica, Jelena Radivojevic, Ivana Z. Matic, Tijana Štajner, Slavica Kneževic-Ušaj, Olgica Djurkovic-Djakovic, and Bogdan A. Šolaja, “Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules,” Journal of the Serbian Chemical Society, vol. 80, no. 11, pp. 1339–1359, 2015. View at Publisher · View at Google Scholar
  • Ruling Shen, Jun Li, Danrong Ye, Qingcheng Wang, and Jian Fei, “Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non–small-cell lung carcinoma and malignant mesothelioma,” Acta Biochimica et Biophysica Sinica, 2016. View at Publisher · View at Google Scholar
  • Yao Zong, Yongguang Yuan, Xiaobing Qian, Zhen Huang, Wei Yang, Leilei Lin, Qishan Zheng, Yujie Li, Huining He, and Qianying Gao, “Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα, and PDGFR Targets,” Scientific Reports, vol. 6, pp. 30843, 2016. View at Publisher · View at Google Scholar
  • M. Ilamathi, P.C. Prabu, K. Ashok Ayyappa, and V. Sivaramakrishnan, “Artesunate obliterates experimental hepatocellular carcinoma in rats through suppression of IL-6-JAK-STAT signalling,” Biomedicine & Pharmacotherapy, vol. 82, pp. 72–79, 2016. View at Publisher · View at Google Scholar
  • Amarish Kumar Yadav, Saripella Srikrishna, and Subash Chandra Gupta, “Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back,” Trends in Pharmacological Sciences, 2016. View at Publisher · View at Google Scholar
  • Yilin Pang, Guiqi Qin, Liping Wu, Xiaoping Wang, and Tongsheng Chen, “Artesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells,” Experimental Cell Research, 2016. View at Publisher · View at Google Scholar
  • Hui-Li Tan, Kok-Gan Chan, Priyia Pusparajah, Surasak Saokaew, Acharaporn Duangjai, Learn-Han Lee, and Bey-Hing Goh, “Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives,” Frontiers in Pharmacology, vol. 7, 2016. View at Publisher · View at Google Scholar
  • Ye Tian, Zhen Liang, Hang Xu, Yanhua Mou, and Chun Guo, “Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry,” Molecules, vol. 21, no. 6, pp. 758, 2016. View at Publisher · View at Google Scholar
  • Roxane Khoogar, Byung-Chang Kim, Jay Morris, and Michael J. Wargovich, “Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal can,” American Journal Of Physiology-Gastrointestinal And Liver Physiology, vol. 310, no. 9, pp. G629–G644, 2016. View at Publisher · View at Google Scholar
  • Ge Xu, Wen-Qin Zou, Shi-Juan Du, Ming-Jun Wu, Ting-Xiu Xiang, and Zi-Guo Luo, “Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis,” Life Sciences, 2016. View at Publisher · View at Google Scholar
  • Rachel P. Abrams, William L. Carroll, and K. A. Woerpel, “Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells,” ACS Chemical Biology, 2016. View at Publisher · View at Google Scholar
  • Anupma Dwivedi, Anisha Mazumder, Lizelle T. Fox, Alicia Brümmer, Minja Gerber, Jan L. du Preez, Richard K. Haynes, and Jeanetta du Plessis, “In vitro skin permeation of artemisone and its nano-vesicular formulations,” International Journal of Pharmaceutics, 2016. View at Publisher · View at Google Scholar
  • Zongru Guo, “Artemisinin anti-malarial drugs in China,” Acta Pharmaceutica Sinica B, 2016. View at Publisher · View at Google Scholar
  • Sangkyu Park, Jun Namkung, Sangtae Oh, and Seokjoon Lee, “Efficient Synthesis and Stimulatory Effect of C-10 Exo-methylene Artemisinin on MC3T3-E1 Preosteoblast Differentiation to Osteoblasts,” Bulletin of the Korean Chemical Society, vol. 37, no. 12, pp. 2058–2061, 2016. View at Publisher · View at Google Scholar
  • Xiaoguang Li, Hui Wang, Tao Chen, Kerong Chen, Jingquan Li, Yu Zhou, Yanling Liu, Xu Zhang, Qian Ba, and Hong Liu, “Preclinical Efficacy and Safety Assessment of Artemisinin-Chemotherapeutic Agent Conjugates for Ovarian Cancer,” EBioMedicine, vol. 14, pp. 44–54, 2016. View at Publisher · View at Google Scholar
  • Kristina Pavić, Petra Gilja, Katja Ester, Marijeta Kralj, Dominique Schols, Dimitra Hadjipavlou-Litina, Eleni Pontiki, Branka Zorc, Ivana Perković, and Filip Kozlina, “Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type,” Molecules, vol. 21, no. 12, 2016. View at Publisher · View at Google Scholar
  • Don W. Coulter, Timothy R. McGuire, John G. Sharp, Erin M. McIntyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R. Alexander, Nagendra K. Chatuverdi, Shantaram S. Joshi, Xiaoyu Chen, and Jonathan L. Vennerstrom, “Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513,” BMC Cancer, vol. 16, no. 1, 2016. View at Publisher · View at Google Scholar
  • Ling Xiao, Hexin Tan, and Lei Zhang, “Artemisia annua glandular secretory trichomes: the biofactory of antimalarial agent artemisinin,” Science Bulletin, vol. 61, no. 1, pp. 26–36, 2016. View at Publisher · View at Google Scholar
  • Brennan, Fairweather, O'Neill, Johnston, Halferty, and Hanna, “Disruption of spermatogenesis in the liver fluke, Fasciola hepatica by two artemisinin derivatives, artemether and artesunate,” Journal of Helminthology, vol. 91, no. 1, pp. 55–71, 2016. View at Publisher · View at Google Scholar
  • Angela R. Guerra, Iola F. Duarte, and Maria F. Duarte, “Role of Isoprenoid Compounds on Angiogenic Regulation: Opportunities and Challenges,” Current Medicinal Chemistry, vol. 23, no. 9, pp. 911–928, 2016. View at Publisher · View at Google Scholar
  • Xiao Chen, Yin Wong, Teck Lim, Wei Lim, Qingsong Lin, Jigang Wang, and Zichun Hua, “Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway,” Molecules, vol. 22, no. 8, pp. 1272, 2017. View at Publisher · View at Google Scholar
  • Bao Ngoc Tran, Hanh Thuy Nguyen, Jong Oh Kim, Chul Soon Yong, and Chien Ngoc Nguyen, “ Developing combination of artesunate with paclitaxel loaded into poly- d,l -lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response ,” Drug Development and Industrial Pharmacy, pp. 1–11, 2017. View at Publisher · View at Google Scholar
  • Asif Raza, Archita Ghoshal, S. Chockalingam, and Siddhartha Sankar Ghosh, “Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells,” Scientific Reports, vol. 7, no. 1, 2017. View at Publisher · View at Google Scholar
  • Yuan-Qiang Hu, Chuan Gao, Shu Zhang, Lei Xu, Zhi Xu, Lian-Shun Feng, Xiang Wu, and Feng Zhao, “Quinoline hybrids and their antiplasmodial and antimalarial activities,” European Journal of Medicinal Chemistry, 2017. View at Publisher · View at Google Scholar
  • Yin Kwan Wong, Chengchao Xu, Karunakaran A. Kalesh, Yingke He, Qingsong Lin, W. S. Fred Wong, Han-Ming Shen, and Jigang Wang, “Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action,” Medicinal Research Reviews, 2017. View at Publisher · View at Google Scholar
  • Chen Sun, and Bing Zhou, “The antimalarial drug artemisinin induces an additional, Sod1-supressible anti-mitochondrial action in yeast,” Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2017. View at Publisher · View at Google Scholar
  • Antonios S. Letis, Ean-Jeong Seo, Sotiris S. Nikolaropoulos, Thomas Efferth, Athanassios Giannis, and Manolis A. Fousteris, “Synthesis and cytotoxic activity of new artemisinin hybrid molecules against human leukemia cells,” Bioorganic & Medicinal Chemistry, 2017. View at Publisher · View at Google Scholar
  • Bing Zhou, Chen Sun, Yu Cao, and Pan Zhu, “A mitochondria-targeting artemisinin derivative with sharply increased antitumor but depressed anti-yeast and anti-malaria activities,” Scientific Reports, vol. 7, 2017. View at Publisher · View at Google Scholar
  • Jessica J. Nunes, Swaroop K. Pandey, Anjali Yadav, Sakshi Goel, and Bushra Ateeq, “Targeting NF-kappa B Signaling by Artesunate Restores Sensitivity of Castrate-Resistant Prostate Cancer Cells to Antiandrogens,” Neoplasia, vol. 19, no. 4, pp. 333–345, 2017. View at Publisher · View at Google Scholar
  • Luis Matías-Hernández, Weimin Jiang, Ke Yang, Kexuan Tang, Peter E. Brodelius, and Soraya Pelaz, “ AaMYB1 and its orthologue AtMYB61 affect terpene metabolism and trichome development in Artemisia annua and Arabidopsis thaliana ,” The Plant Journal, vol. 90, no. 3, pp. 520–534, 2017. View at Publisher · View at Google Scholar
  • Jing Yang, Zhengchao Tu, Xin Xu, Jinfeng Luo, Xing Yan, Chongzhao Ran, Xinliang Mao, Ke Ding, and Chunhua Qiao, “Novel conjugates of endoperoxide and 4-anilinoquinazoline as potential anticancer agents,” Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 6, pp. 1341–1345, 2017. View at Publisher · View at Google Scholar
  • Subramanian Natesan, Chandrasekar Ponnusamy, Abimanyu Sugumaran, Senthilkumar Chelladurai, Sharavanan Shanmugam Palaniappan, and Rajaguru Palanichamy, “Artemisinin loaded chitosan magnetic nanoparticles for the efficient targeting to the breast cancer,” International Journal of Biological Macromolecules, 2017. View at Publisher · View at Google Scholar
  • Lin Hou, Xiaoning Shan, Lisha Hao, Qianhua Feng, and Zhenzhong Zhang, “Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform,” Acta Biomaterialia, 2017. View at Publisher · View at Google Scholar
  • Archana Bhaw-Luximon, and Dhanjay Jhurry, “Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives,” Cancer Chemotherapy and Pharmacology, vol. 79, no. 3, pp. 451–466, 2017. View at Publisher · View at Google Scholar
  • Liping Wu, Yilin Pang, Tongsheng Chen, Guiqi Qin, Gaina Xi, Shengnan Wu, and Xiaoping Wang, “Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives,” PLoS ONE, vol. 12, no. 2, 2017. View at Publisher · View at Google Scholar
  • Axel Griesbeck, Maria Bräutigam, Margarethe Kleczka, and Angela Raabe, “Synthetic Approaches to Mono- and Bicyclic Perortho-Esters with a Central 1,2,4-Trioxane Ring as the Privileged Lead Structure in Antimalarial and Antitumor-Active Peroxides and Clarification of the Peroxide Relevance,” Molecules, vol. 22, no. 1, pp. 119, 2017. View at Publisher · View at Google Scholar