Combination Therapies of Artemisinin and its Derivatives as a Viable Approach for Future Cancer Treatment

Author(s): Maushmi S. Kumar, Tanuja T. Yadav, Rohan R. Khair, Godefridus J. Peters, Mayur C. Yergeri*

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 31 , 2019

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Abstract:

Background: Many anticancer drugs have been developed for clinical usage till now, but the major problem is the development of drug-resistance over a period of time in the treatment of cancer. Anticancer drugs produce huge adverse effects, ultimately leading to death of the patient. Researchers have been focusing on the development of novel molecules with higher efficacy and lower toxicity; the anti-malarial drug artemisinin and its derivatives have exhibited cytotoxic effects.

Methods: We have done extensive literature search for artemisinin for its new role as anti-cancer agent for future treatment. Last two decades papers were referred for deep understanding to strengthen its role.

Result: Literature shows changes at 9, 10 position in the artemisinin structure produces anticancer activity. Artemisinin shows anticancer activity in leukemia, hepatocellular carcinoma, colorectal and breast cancer cell lines. Artemisinin and its derivatives have been studied as combination therapy with several synthetic compounds, RNA interfaces, recombinant proteins and antibodies etc., for synergizing the effect of these drugs. They produce an anticancer effect by causing cell cycle arrest, regulating signaling in apoptosis, angiogenesis and cytotoxicity activity on the steroid receptors. Many novel formulations of artemisinin are being developed in the form of carbon nanotubes, polymer-coated drug particles, etc., for delivering artemisinin, since it has poor water/ oil solubility and is chemically unstable.

Conclusion: We have summarize the combination therapies of artemisinin and its derivatives with other anticancer drugs and also focussed on recent developments of different drug delivery systems in the last 10 years. Various reports and clinical trials of artemisinin type drugs indicated selective cytotoxicity along with minimal toxicity thus projecting them as promising anti-cancer agents in future cancer therapies.

Keywords: Artemisinin, anticancer properties, reactive oxygen species, repurposing, formulations, combination therapy.

[1]
Sudhakar A. History of cancer, ancient and modern treatment methods. J Cancer Sci Ther 2009; 1(2): 1-4.
[http://dx.doi.org/10.4172/1948-5956.100000e2] [PMID: 20740081]
[2]
O’Connor HJ. Helicobacter pylori and gastro-oesophageal reflux disease-clinical implications and management. Aliment Pharmacol Ther 1999; 13(2): 117-27.
[http://dx.doi.org/10.1046/j.1365-2036.1999.00460.x] [PMID: 10102940]
[3]
Rajpal S, Kumar A, Joe W. Economic burden of cancer in India: evidence from cross-sectional nationally representative household survey, 2014. PLoS One 2018; 13(2) e0193320
[http://dx.doi.org/10.1371/journal.pone.0193320] [PMID: 29481563]
[4]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68(1): 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[5]
Keenan J, Murphy L, Henry M, Meleady P, Clynes M. Proteomic analysis of multidrug-resistance mechanisms in adriamycin-resistant variants of DLKP, a squamous lung cancer cell line. Proteomics 2009; 9(6): 1556-66.
[http://dx.doi.org/10.1002/pmic.200800633] [PMID: 19242932]
[6]
Efferth T. The human ATP-binding cassette transporter genes: from the bench to the bedside. Curr Mol Med 2001; 1(1): 45-65.
[http://dx.doi.org/10.2174/1566524013364194] [PMID: 11899242]
[7]
Gillet JP, Efferth T, Remacle J. Chemotherapy-induced resistance by ATP-binding cassette transporter genes. Biochim Biophys Acta 2007; 1775(2): 237-62.
[PMID: 17572300]
[8]
Amin ML. P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights 2013; 7: 27-34.
[http://dx.doi.org/10.4137/DTI.S12519] [PMID: 24023511]
[9]
Xue X, Liang X-J. Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology. Chin J Cancer 2012; 31(2): 100-9.
[http://dx.doi.org/10.5732/cjc.011.10326] [PMID: 22237039]
[10]
Hodges LM1, Markova SM, Chinn LW, et al. Very important pharmacogene summary: ABCB1 (MDR1, P- glycoprotein). Pharmacogenet Genomics 2011; 21: 152-61.
[11]
Rosenberg MF, Bikadi Z, Chan J, et al. The human breast cancer resistance protein (BCRP/ABCG2) shows conformational changes with mitoxantrone. Structure 2010; 18(4): 482-93.
[http://dx.doi.org/10.1016/j.str.2010.01.017] [PMID: 20399185]
[12]
Noguchi K, Katayama K, Sugimoto Y. Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics. Pharm Genomics Pers Med 2014; 7: 53-64.
[http://dx.doi.org/10.2147/PGPM.S38295] [PMID: 24523596]
[13]
Das AK. Anticancer effect of antimalarial artemisinin compounds. Ann Med Health Sci Res 2015; 5(2): 93-102.
[http://dx.doi.org/10.4103/2141-9248.153609] [PMID: 25861527]
[14]
Bhaw-Luximon A, Jhurry D. Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives. Cancer Chemother Pharmacol 2017; 79(3): 451-66.
[http://dx.doi.org/10.1007/s00280-017-3251-7] [PMID: 28210763]
[15]
Pritchard JR, Lauffenburger DA, Hemann MT. Understanding resistance to combination chemotherapy. Drug Resist Updat 2012; 15(5-6): 249-57.
[http://dx.doi.org/10.1016/j.drup.2012.10.003] [PMID: 23164555]
[16]
Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotechnol 2012; 2012247597
[http://dx.doi.org/10.1155/2012/247597] [PMID: 22174561]
[17]
Correia MA, Sinclair PR, De Matteis F. Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal. Drug Metab Rev 2011; 43(1): 1-26.
[http://dx.doi.org/10.3109/03602532.2010.515222] [PMID: 20860521]
[18]
Meshnick SR. Artemisinin antimalarials: mechanisms of action and resistance. Med Trop (Mars) 1998; 58(3)(Suppl.): 13-7.
[PMID: 10212891]
[19]
Ellis DS, Li ZL, Gu HM, et al. The chemotherapy of rodent malaria, XXXIX. Ultrastructural changes following treatment with artemisinine of Plasmodium berghei infection in mice, with observations of the localization of [3H]-dihydroartemisinine in P. falciparum in vitro. Ann Trop Med Parasitol 1985; 79(4): 367-74.
[http://dx.doi.org/10.1080/00034983.1985.11811933] [PMID: 3907556]
[20]
Jung M, Kim H, Nam KY, No KT. Three-dimensional structure of Plasmodium falciparum Ca2+-ATPase(PfATP6) and docking of artemisinin derivatives to PfATP6. Bioorg Med Chem Lett 2005; 15(12): 2994-7.
[http://dx.doi.org/10.1016/j.bmcl.2005.04.041] [PMID: 15908211]
[21]
White NJ. Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob Agents Chemother 1997; 41(7): 1413-22.
[http://dx.doi.org/10.1128/AAC.41.7.1413] [PMID: 9210658]
[22]
Eckstein-Ludwig U, Webb RJ, Van Goethem IDA, et al. Artemisinins target the SERCA of Plasmodium falciparum. Nature 2003; 424(6951): 957-61.
[http://dx.doi.org/10.1038/nature01813] [PMID: 12931192]
[23]
N N C GP, Chakraborty C. Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach. Sci Rep 2016; 6: 30106.
[http://dx.doi.org/10.1038/srep30106] [PMID: 27471101]
[24]
O’Neill PM, Barton VE, Ward SA. The molecular mechanism of action of artemisinin--the debate continues. Molecules 2010; 15(3): 1705-21.
[http://dx.doi.org/10.3390/molecules15031705] [PMID: 20336009]
[25]
Slezakova S, Ruda-Kucerova J. Anticancer activity of artemisinin and its derivatives. Anticancer Res 2017; 37(11): 5995-6003.
[PMID: 29061778]
[26]
Nakase I, Gallis B, Takatani-Nakase T, et al. Transferrin receptor-dependent cytotoxicity of artemisinin-transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer Lett 2009; 274(2): 290-8.
[http://dx.doi.org/10.1016/j.canlet.2008.09.023] [PMID: 19006645]
[27]
Badshah SL, Ullah A, Ahmad N, Almarhoon ZM, Mabkhot Y. Increasing the strength and production of artemisinin and its derivatives. Molecules 2018; 23(1) e100
[http://dx.doi.org/10.3390/molecules23010100] [PMID: 29301383]
[28]
Zhang Y, Xu G, Zhang S, Wang D, Saravana Prabha P, Zuo Z. Antitumor research on artemisinin and its bioactive derivatives. Nat Prod Bioprospect 2018; 8(4): 303-19.
[http://dx.doi.org/10.1007/s13659-018-0162-1] [PMID: 29633188]
[29]
Novak B, Sible JC, Tyson JJ. Checkpoints in the cell cycle. Encyclopedia of Life Sciences 2002; 1-8.
[30]
Efferth T, Sauerbrey A, Olbrich A, et al. Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 2003; 64(2): 382-94.
[http://dx.doi.org/10.1124/mol.64.2.382] [PMID: 12869643]
[31]
Hou J, Wang D, Zhang R, Wang H. Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action. Clin Cancer Res 2008; 14(17): 5519-30.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0197] [PMID: 18765544]
[32]
Wang S-J, Gao Y, Chen H, et al. Dihydroartemisinin inactivates NF-kappaB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Lett 2010; 293(1): 99-108.
[http://dx.doi.org/10.1016/j.canlet.2010.01.001] [PMID: 20137856]
[33]
Yao L, Xie H, Jin Q-Y, Hu W-L, Chen L-J. [Analyzing anti-cancer action mechanisms of dihydroartemisinin using gene chip] Zhongguo Zhongyao Zazhi 2008; 33(13): 1583-6.
[PMID: 18837321]
[34]
Jiao Y, Ge CM, Meng QH, Cao JP, Tong J, Fan SJ. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin 2007; 28(7): 1045-56.
[http://dx.doi.org/10.1111/j.1745-7254.2007.00612.x] [PMID: 17588342]
[35]
Uren AG, Wong L, Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol 2000; 10(21): 1319-28.
[http://dx.doi.org/10.1016/S0960-9822(00)00769-7] [PMID: 11084331]
[36]
Xu Q, Li ZX, Peng HQ, et al. Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo. J Zhejiang Univ Sci B 2011; 12(4): 247-55.
[http://dx.doi.org/10.1631/jzus.B1000373] [PMID: 21462379]
[37]
Youns M, Efferth T, Reichling J, Fellenberg K, Bauer A, Hoheisel JD. Gene expression profiling identifies novel key players involved in the cytotoxic effect of artesunate on pancreatic cancer cells. Biochem Pharmacol 2009; 78(3): 273-83.
[http://dx.doi.org/10.1016/j.bcp.2009.04.014] [PMID: 19393226]
[38]
Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotechnol 2012; 2012247597
[http://dx.doi.org/10.1155/2012/247597] [PMID: 22174561]
[39]
Li Z, Li Q, Wu J, Wang M, Yu J. Artemisinin and its derivatives as a repurposing anticancer agent: what else do we need to do? Molecules 2016; 21(10): 1-14.
[http://dx.doi.org/10.3390/molecules21101331] [PMID: 27739410]
[40]
Zhao M, Xue DB, Zheng B, Zhang WH, Pan SH, Sun B. Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis. World J Gastroenterol 2007; 13(42): 5612-7.
[http://dx.doi.org/10.3748/wjg.v13.i42.5612] [PMID: 17948936]
[41]
Peixoto PM, Lue JK, Ryu SY, Wroble BN, Sible JC, Kinnally KW. Mitochondrial apoptosis-induced channel (MAC) function triggers a Bax/Bak-dependent bystander effect. Am J Pathol 2011; 178(1): 48-54.
[http://dx.doi.org/10.1016/j.ajpath.2010.11.014] [PMID: 21224042]
[42]
Mondal A, Chatterji U. Artemisinin represses telomerase subunits and induces apoptosis in HPV-39 infected human cervical cancer cells. J Cell Biochem 2015; 116(9): 1968-81.
[http://dx.doi.org/10.1002/jcb.25152] [PMID: 25755006]
[43]
Zhang C, Zhang Z, Zhu Y, Qin S. Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer. Anticancer Agents Med Chem 2014; 14(2): 280-9.
[http://dx.doi.org/10.2174/18715206113136660337] [PMID: 24066844]
[44]
Zhang J-L, Wang Z, Hu W, Chen S-S, Lou X-E, Zhou H-J. DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma. Microvasc Res 2013; 87: 14-24.
[http://dx.doi.org/10.1016/j.mvr.2013.02.006] [PMID: 23466284]
[45]
Elf S, Lin R, Xia S, et al. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. Oncogene 2017; 36(2): 254-62.
[http://dx.doi.org/10.1038/onc.2016.196] [PMID: 27270429]
[46]
Wang D, Meng G, Zheng M, et al. The glutaminase-1 inhibitor 968 enhances dihydroartemisinin-mediated antitumor efficacy in hepatocellular carcinoma cells. PLoS One 2016; 11(11) e0166423
[http://dx.doi.org/10.1371/journal.pone.0166423] [PMID: 27835669]
[47]
Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012; 75(3): 311-35.
[http://dx.doi.org/10.1021/np200906s] [PMID: 22316239]
[48]
Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79(3): 629-61.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[49]
Stevens JJ, Graham B, Walker AM, Tchounwou PB, Rogers C. The effects of arsenic trioxide on DNA synthesis and genotoxicity in human colon cancer cells. Int J Environ Res Public Health 2010; 7(5): 2018-32.
[http://dx.doi.org/10.3390/ijerph7052018] [PMID: 20623008]
[50]
Ismail HM, Barton V, Phanchana M, et al. Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7. Proc Natl Acad Sci USA 2016; 113(8): 2080-5.
[http://dx.doi.org/10.1073/pnas.1600459113] [PMID: 26858419]
[51]
Kapoor S. Artesunate and its emerging anti-neoplastic effects: beyond its role in attenuating tumor growth in osteosarcomas. J Zhejiang Univ Sci B 2012; 13(12): 1029-30.
[http://dx.doi.org/10.1631/jzus.B1200288] [PMID: 23225859]
[52]
Dadgar N, Alavi SE, Esfahani MK, Akbarzadeh A. Study of toxicity effect of pegylated nanoliposomal artemisinin on breast cancer cell line. Indian J Clin Biochem 2013; 28(4): 410-2.
[http://dx.doi.org/10.1007/s12291-013-0306-3] [PMID: 24426245]
[53]
Hooft van Huijsduijnen R, Guy RK, Chibale K, et al. Anticancer properties of distinct antimalarial drug classes. PLoS One 2013; 8(12) e82962
[http://dx.doi.org/10.1371/journal.pone.0082962] [PMID: 24391728]
[54]
Dwivedi A, Mazumder A, du Plessis L, du Preez JL, Haynes RK, du Plessis J. In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells. Nanomedicine (Lond) 2015; 11(8): 2041-50.
[http://dx.doi.org/10.1016/j.nano.2015.07.010] [PMID: 26282380]
[55]
Chen X, Wong YK, Lim TK, et al. Artesunate activates the intrinsic apoptosis of HCT116 cells through the suppression of fatty acid synthesis and the NF-κB pathway. Molecules 2017; 22(8) e1272
[http://dx.doi.org/10.3390/molecules22081272] [PMID: 28786914]
[56]
Ackermann A, Karagöz AÇ, Ghoochani A, et al. Cytotoxic profiling of artesunic and betulinic acids and their synthetic hybrid compound on neurons and gliomas. Oncotarget 2017; 8(37): 61457-74.
[http://dx.doi.org/10.18632/oncotarget.18390] [PMID: 28977877]
[57]
Zhou Y, Wang X, Zhang J, et al. Artesunate suppresses the viability and mobility of prostate cancer cells through UCA1, the sponge of miR-184. Oncotarget 2017; 8(11): 18260-70.
[http://dx.doi.org/10.18632/oncotarget.15353] [PMID: 28209917]
[58]
Tran TH, Nguyen TD, Poudel BK, et al. Development and evaluation of artesunate-loaded chitosan-coated lipid nanocapsule as a potential drug delivery system against breast cancer. AAPS PharmSciTech 2015; 16(6): 1307-16.
[http://dx.doi.org/10.1208/s12249-015-0311-3] [PMID: 25787869]
[59]
Luan S, Zhong H, Zhao X, et al. Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin. Eur J Med Chem 2017; 141: 584-95.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.023] [PMID: 29102180]
[60]
Lucibello M, Adanti S, Antelmi E, et al. Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells. Oncotarget 2015; 6(7): 5275-91.
[http://dx.doi.org/10.18632/oncotarget.2971] [PMID: 25779659]
[61]
Zhang CZ, Pan Y, Cao Y, et al. Histone deacetylase inhibitors facilitate dihydroartemisinin-induced apoptosis in liver cancer in vitro and in vivo. PLoS One 2012; 7(6) e39870
[http://dx.doi.org/10.1371/journal.pone.0039870] [PMID: 22761917]
[62]
Wu L, Pang Y, Qin G, et al. Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives. PLoS One 2017; 12(2) e0171840
[http://dx.doi.org/10.1371/journal.pone.0171840] [PMID: 28182780]
[63]
Lu M, Sun L, Zhou J, Yang J. Dihydroartemisinin induces apoptosis in colorectal cancer cells through the mitochondria-dependent pathway. Tumour Biol 2014; 35(6): 5307-14.
[http://dx.doi.org/10.1007/s13277-014-1691-9] [PMID: 24519064]
[64]
Krishna S, Ganapathi S, Ster IC, et al. A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine 2014; 2(1): 82-90.
[http://dx.doi.org/10.1016/j.ebiom.2014.11.010] [PMID: 26137537]
[65]
Dobler M, Weder C, Ahumada O, Neuenschwander P, Suter UW. Local motion in NLO main-chain polymers with enhanced orientational stability. Polym Mater Sci Eng 1997; 76: 308-9.
[66]
Zhou X, Sun WJ, Wang WM, et al. Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo. Anticancer Drugs 2013; 24(9): 920-7.
[http://dx.doi.org/10.1097/CAD.0b013e328364a109] [PMID: 23958790]
[67]
Li XY, Zhao Y, Sun MG, et al. Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma. Biomaterials 2014; 35(21): 5591-604.
[http://dx.doi.org/10.1016/j.biomaterials.2014.03.049] [PMID: 24726749]
[68]
Wu B, Hu K, Li S, et al. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer. Oncol Rep 2012; 27(1): 101-8.
[PMID: 22025319]
[69]
Farsam V, Hassan ZM, Zavaran-Hosseini A, Noori S, Mahdavi M, Ranjbar M. Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo. Int Immunopharmacol 2011; 11(11): 1802-8.
[http://dx.doi.org/10.1016/j.intimp.2011.07.008] [PMID: 21824530]
[70]
Noori S, Hassan ZM. Dihydroartemisinin shift the immune response towards Th1, inhibit the tumor growth in vitro and in vivo. Cell Immunol 2011; 271(1): 67-72.
[http://dx.doi.org/10.1016/j.cellimm.2011.06.008] [PMID: 21820106]
[71]
Zhu XX, Yang L, Li YJ, et al. Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis. Pharmacol Rep 2013; 65(2): 410-20.
[http://dx.doi.org/10.1016/S1734-1140(13)71016-8] [PMID: 23744425]
[72]
Moon DK, Singhal V, Kumar N, Shapiro TA, Posner GH. Antimalarial preclinical drug development: a single oral dose of a 5-carbon-linked trioxane dimer plus mefloquine cures malaria-infected mice. Drug Dev Res 2009; 71(1): 76-81.
[http://dx.doi.org/10.1002/ddr.20350] [PMID: 20686674]
[73]
Letis AS, Seo EJ, Nikolaropoulos SS, Efferth T, Giannis A, Fousteris MA. Synthesis and cytotoxic activity of new artemisinin hybrid molecules against human leukemia cells. Bioorg Med Chem 2017; 25(13): 3357-67.
[http://dx.doi.org/10.1016/j.bmc.2017.04.021] [PMID: 28456567]
[74]
Zhang L, Chen F, Zhang Z, Chen Y, Wang J. Synthesis and biological evaluation of a novel artesunate-podophyllotoxin conjugate as anticancer agent. Bioorg Med Chem Lett 2016; 26(1): 38-42.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.042] [PMID: 26615886]
[75]
Joubert JP, Smit FJ, du Plessis L, Smith PJ, N’Da DD. Synthesis and in vitro biological evaluation of aminoacridines and artemisinin-acridine hybrids. Eur J Pharm Sci 2014; 56: 16-27.
[http://dx.doi.org/10.1016/j.ejps.2014.01.014] [PMID: 24560941]
[76]
Wei M, Xu J, Zhang H, Li X. Synthesis and anti-tumor effect of artemisone derivatives. Youji Huaxue 2015; 35: 1097.
[http://dx.doi.org/10.6023/cjoc201409039]
[77]
Soomro S, Langenberg T, Mahringer A, et al. Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties. J Cell Mol Med 2011; 15(5): 1122-35.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01120.x] [PMID: 20629994]
[78]
Xu C-C, Deng T, Fan M-L, Lv W-B, Liu J-H, Yu B-Y. Synthesis and in vitro antitumor evaluation of dihydroartemisinin-cinnamic acid ester derivatives. Eur J Med Chem 2016; 107: 192-203.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.003] [PMID: 26595184]
[79]
Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B. Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther 2011; 10(12): 2224-33.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0534] [PMID: 21998290]
[80]
Aquino I, Tsuboy MSF, Marcarini JC, Mantovani MS, Perazzo FF, Maistro EL. Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions. Genet Mol Res 2013; 12(3): 2517-27.
[http://dx.doi.org/10.4238/2013.July.24.6] [PMID: 23979886]
[81]
Kim BH, Kim HJ, Wu HG, et al. Role of postoperative radiotherapy after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small-cell lung cancer: a propensity score matching analysis. Clin Lung Cancer 2014; 15(5): 356-64.
[http://dx.doi.org/10.1016/j.cllc.2014.05.005] [PMID: 24996882]
[82]
Falchook AD, Green R, Knowles ME, et al. Comparison of patient- and practitioner-reported toxic effects associated with chemoradiotherapy for head and neck cancer. JAMA Otolaryngol Head Neck Surg 2016; 142(6): 517-23.
[http://dx.doi.org/10.1001/jamaoto.2016.0656] [PMID: 27149571]
[83]
White R, Dinneen T, Makris A. Local radiotherapy alone following neoadjuvant chemotherapy and surgery in combined clinical stage II and III breast cancer. Radiat Oncol 2016; 11: 93.
[http://dx.doi.org/10.1186/s13014-016-0670-2] [PMID: 27457764]
[84]
Krusche B, Arend J, Efferth T. Synergistic inhibition of angiogenesis by artesunate and captopril in vitro and in vivo. Evid Based Complement Alternat Med 2013; 2013454783
[http://dx.doi.org/10.1155/2013/454783] [PMID: 24223058]
[85]
Shahbazfar AA, Zare P, Ranjbaran M, et al. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines. J Cancer Res Ther 2014; 10(4): 1057-62.
[http://dx.doi.org/10.4103/0973-1482.137975] [PMID: 25579554]
[86]
Ganguli A, Choudhury D, Datta S, Bhattacharya S, Chakrabarti G. Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis. Biochimie 2014; 107(Pt B): 338-49.
[http://dx.doi.org/10.1016/j.biochi.2014.10.001] [PMID: 25308836]
[87]
Xu SN, Wang TS, Li X, Wang YP. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation. Sci Rep 2016; 6: 32734.
[http://dx.doi.org/10.1038/srep32734] [PMID: 27586085]
[88]
Hu Y-J, Zhang J-Y, Luo Q, et al. Nanostructured dihydroartemisinin plus epirubicin liposomes enhance treatment efficacy of breast cancer by inducing autophagy and apoptosis. Nanomaterials (Basel) 2018; 8(10): 804.
[http://dx.doi.org/10.3390/nano8100804] [PMID: 30304783]
[89]
Zhang C, Zhang Z, Zhu Y, Qin S. Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer. Anticancer Agents Med Chem 2014; 14(2): 280-9.
[http://dx.doi.org/10.2174/18715206113136660337] [PMID: 24066844]
[90]
Wang X, Wu G, Cao G, et al. Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells. Mol Med Rep 2015; 12(3): 4620-5.
[http://dx.doi.org/10.3892/mmr.2015.3995] [PMID: 26126921]
[91]
Elf S, Lin R, Xia S, et al. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. Oncogene 2017; 36(2): 254-62.
[http://dx.doi.org/10.1038/onc.2016.196] [PMID: 27270429]
[92]
Wang D, Meng G, Zheng M, et al. The glutaminase-1 inhibitor 968 enhances dihydroartemisinin-mediated antitumor efficacy in hepatocellular carcinoma cells. PLoS One 2016; 11(11) e0166423
[http://dx.doi.org/10.1371/journal.pone.0166423] [PMID: 27835669]
[93]
Sieber S, Gdynia G, Roth W, Bonavida B, Efferth T. Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. Int J Oncol 2009; 35(1): 149-58.
[PMID: 19513562]
[94]
Wang YB, Hu Y, Li Z, et al. Artemether combined with shRNA interference of vascular cell adhesion molecule-1 significantly inhibited the malignant biological behavior of human glioma cells. PLoS One 2013; 8(4) e60834
[http://dx.doi.org/10.1371/journal.pone.0060834] [PMID: 23593320]
[95]
Wu J, Hu D, Zhang R. Depletion of Bmi-1 enhances 5-fluorouracil-induced apoptosis and autophagy in hepatocellular carcinoma cells. Oncol Lett 2012; 4(4): 723-6.
[http://dx.doi.org/10.3892/ol.2012.805] [PMID: 23205090]
[96]
Dawood M, Hamdoun S, Efferth T. Multifactorial modes of action of arsenic trioxide in cancer cells as analyzed by classical and network pharmacology. Front Pharmacol 2018; 9: 143.
[http://dx.doi.org/10.3389/fphar.2018.00143] [PMID: 29535630]
[97]
Papanikolaou X, Johnson S, Garg T, et al. Artesunate overcomes drug resistance in multiple myeloma by inducing mitochondrial stress and non-caspase apoptosis. Oncotarget 2014; 5(12): 4118-28.
[http://dx.doi.org/10.18632/oncotarget.1847] [PMID: 24948357]
[98]
Wang B, Hou D, Liu Q, et al. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther 2015; 16(10): 1548-56.
[http://dx.doi.org/10.1080/15384047.2015.1071738] [PMID: 26176175]
[99]
Quiros S, Roos WP, Kaina B. Rad51 and BRCA2--New molecular targets for sensitizing glioma cells to alkylating anticancer drugs. PLoS One 2011; 6(11) e27183
[http://dx.doi.org/10.1371/journal.pone.0027183] [PMID: 22073281]
[100]
Kast RE, Ellingson BM, Marosi C, Halatsch ME. Glioblastoma treatment using perphenazine to block the subventricular zone’s tumor trophic functions. J Neurooncol 2014; 116(2): 207-12.
[http://dx.doi.org/10.1007/s11060-013-1308-y] [PMID: 24242756]
[101]
Roh JL, Kim EH, Jang H, Shin D. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol 2017; 11: 254-62.
[http://dx.doi.org/10.1016/j.redox.2016.12.010] [PMID: 28012440]
[102]
Wu J, Hu D, Yang G, et al. Down-regulation of BMI-1 cooperates with artemisinin on growth inhibition of nasopharyngeal carcinoma cells. J Cell Biochem 2011; 112(7): 1938-48.
[http://dx.doi.org/10.1002/jcb.23114] [PMID: 21445878]
[103]
Wu GS, Lu JJ, Guo JJ, et al. Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells. Pharmacol Rep 2013; 65(2): 453-9.
[http://dx.doi.org/10.1016/S1734-1140(13)71021-1] [PMID: 23744430]
[104]
Feng X, Li L, Jiang H, Jiang K, Jin Y, Zheng J. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy. Biochem Biophys Res Commun 2014; 444(3): 376-81.
[http://dx.doi.org/10.1016/j.bbrc.2014.01.053] [PMID: 24462866]
[105]
Drenberg CD, Buaboonnam J, Orwick SJ, et al. Evaluation of artemisinins for the treatment of acute myeloid leukemia. Cancer Chemother Pharmacol 2016; 77(6): 1231-43.
[http://dx.doi.org/10.1007/s00280-016-3038-2] [PMID: 27125973]
[106]
Zhao X, Guo X, Yue W, Wang J, Yang J, Chen J. Artemether suppresses cell proliferation and induces apoptosis in diffuse large B cell lymphoma cells. Exp Ther Med 2017; 14(5): 4083-90.
[http://dx.doi.org/10.3892/etm.2017.5063] [PMID: 29104626]
[107]
Chan HW, Singh NP, Lai HC. Cytotoxicity of dihydroartemisinin toward Molt-4 cells attenuated by N-tert-butyl-alpha-phenylnitrone and deferoxamine. Anticancer Res 2013; 33(10): 4389-93.
[PMID: 24123007]
[108]
Huo L, Wei W, Wu S, et al. Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells. Exp Ther Med 2018; 15(3): 3059-65.
[http://dx.doi.org/10.3892/etm.2018.5784] [PMID: 29599840]
[109]
Gravett AM, Liu WM, Krishna S, et al. In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents. Cancer Chemother Pharmacol 2011; 67(3): 569-77.
[http://dx.doi.org/10.1007/s00280-010-1355-4] [PMID: 20490800]
[110]
Horwedel C, Tsogoeva SB, Wei S, Efferth T. Cytotoxicity of artesunic acid homo- and heterodimer molecules toward sensitive and multidrug-resistant CCRF-CEM leukemia cells. J Med Chem 2010; 53(13): 4842-8.
[http://dx.doi.org/10.1021/jm100404t] [PMID: 20527917]
[111]
Wang YB, Hu Y, Li Z, et al. Artemether combined with shRNA interference of vascular cell adhesion molecule-1 significantly inhibited the malignant biological behavior of human glioma cells. PLoS One 2013; 8(4) e60834
[http://dx.doi.org/10.1371/journal.pone.0060834] [PMID: 23593320]
[112]
Isacchi B, Arrigucci S, la Marca G, et al. Conventional and long-circulating liposomes of artemisinin: preparation, characterization, and pharmacokinetic profile in mice. J Liposome Res 2011; 21(3): 237-44.
[http://dx.doi.org/10.3109/08982104.2010.539185] [PMID: 21158702]
[113]
Chen HJ, Huang XR, Zhou XB, Zheng BY, Huang JD. Potential sonodynamic anticancer activities of artemether and liposome-encapsulated artemether. Chem Commun (Camb) 2015; 51(22): 4681-4.
[http://dx.doi.org/10.1039/C5CC00927H] [PMID: 25691357]
[114]
Want MY, Islammudin M, Chouhan G, et al. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis. Int J Nanomedicine 2017; 12: 2189-204.
[http://dx.doi.org/10.2147/IJN.S106548] [PMID: 28356736]
[115]
Jin M, Shen X, Zhao C, et al. In vivo study of effects of artesunate nanoliposomes on human hepatocellular carcinoma xenografts in nude mice. Drug Deliv 2013; 20(3-4): 127-33.
[http://dx.doi.org/10.3109/10717544.2013.801047] [PMID: 23731485]
[116]
Righeschi C, Coronnello M, Mastrantoni A, et al. Strategy to provide a useful solution to effective delivery of dihydroartemisinin: development, characterization and in vitro studies of liposomal formulations. Colloids Surf B Biointerfaces 2014; 116: 121-7.
[http://dx.doi.org/10.1016/j.colsurfb.2013.12.019] [PMID: 24462780]
[117]
Efferth T. Expanding the therapeutic spectrum of artemisinin: activity against infectious diseases beyond malaria and novel pharmaceutical developments. World J Tradit Chin Med 2016; 2: 1-23.
[http://dx.doi.org/10.15806/j.issn.2311-8571.2016.0002]
[118]
Mhlwatika Z, Aderibigbe BA. Polymeric nanocarriers for the delivery of antimalarials. Molecules 2018; 23(10): 2527.
[http://dx.doi.org/10.3390/molecules23102527] [PMID: 30279405]
[119]
Bhadra D, Bhadra S, Jain NK. Pegylated lysine based copolymeric dendritic micelles for solubilization and delivery of artemether. J Pharm Pharm Sci 2005; 8(3): 467-82.
[PMID: 16401394]
[120]
Lu WF, Chen SF, Wen ZY, Li Q, Chen JH. In vitro evaluation of efficacy of dihydroartemisinin-loaded methoxy poly(ethylene glycol)/poly(L-lactic acid) amphiphilic block copolymeric micelles. J Appl Polym Sci 2013; 128: 3084-92.
[http://dx.doi.org/10.1002/app.38518]
[121]
Wang Z, Yu Y, Ma J, et al. LyP-1 modification to enhance delivery of artemisinin or fluorescent probe loaded polymeric micelles to highly metastatic tumor and its lymphatics. Mol Pharm 2012; 9(9): 2646-57.
[http://dx.doi.org/10.1021/mp3002107] [PMID: 22853186]
[122]
Kothamasu P, Kanumur H, Ravur N, Maddu C, Parasuramrajam R, Thangavel S. Nanocapsules: the weapons for novel drug delivery systems. Bioimpacts 2012; 2(2): 71-81.
[PMID: 23678444]
[123]
Chen Y, Lin X, Park H, Greever R. Study of artemisinin nanocapsules as anticancer drug delivery systems. Nanomedicine (Lond) 2009; 5(3): 316-22.
[http://dx.doi.org/10.1016/j.nano.2008.12.005] [PMID: 19523432]
[124]
Tran TH, Nguyen TD, Poudel BK, et al. Development and evaluation of artesunate-loaded chitosan-coated lipid nanocapsule as a potential drug delivery system against breast cancer. AAPS PharmSciTech 2015; 16(6): 1307-16.
[http://dx.doi.org/10.1208/s12249-015-0311-3] [PMID: 25787869]
[125]
Sanchis J, Canal F, Lucas R, Vicent MJ. Polymer-drug conjugates for novel molecular targets. Nanomedicine (Lond) 2010; 5(6): 915-35.
[http://dx.doi.org/10.2217/nnm.10.71] [PMID: 20735226]
[126]
Duro-Castano A, Conejos-Sánchez I, Vicent MJ. Peptide-based polymer therapeutics. Polymers (Basel) 2014; 6: 515-51.
[http://dx.doi.org/10.3390/polym6020515]
[127]
Wang D, Li H, Gu J, et al. Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. J Pharm Biomed Anal 2013; 83: 141-8.
[http://dx.doi.org/10.1016/j.jpba.2013.05.001] [PMID: 23732534]
[128]
Zhang X, Ba Q, Gu Z, et al. Fluorescent coumarin-artemisinin conjugates as mitochondria-targeting theranostic probes for enhanced anticancer activities. Chemistry 2015; 21(48): 17415-21.
[http://dx.doi.org/10.1002/chem.201502543] [PMID: 26458147]
[129]
Fan J, Zeng F, Xu J, Wu S. Targeted anti-cancer prodrug based on carbon nanotube with photodynamic therapeutic effect and pH-triggered drug release. J Nanopart Res 2013; 15: 1911.
[http://dx.doi.org/10.1007/s11051-013-1911-z]
[130]
Zhang H, Hou L, Jiao X, Ji Y, Zhu X, Zhang Z. Transferrin-mediated fullerenes nanoparticles as Fe(2+)-dependent drug vehicles for synergistic anti-tumor efficacy. Biomaterials 2015; 37: 353-66.
[http://dx.doi.org/10.1016/j.biomaterials.2014.10.031] [PMID: 25453964]
[131]
Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C. Solid lipid nanoparticles for targeted brain drug delivery. Adv Drug Deliv Rev 2007; 59(6): 454-77.
[http://dx.doi.org/10.1016/j.addr.2007.04.011] [PMID: 17570559]
[132]
Singh S, Singh Kamal S, Sharma A, Kaur D, Kumar Katual M, Kumar R. Formulation and in-vitro evaluation of solid lipid nanoparticles containing levosulpiride. Open Nanomed J 2017; 04: 17-29.
[http://dx.doi.org/10.2174/1875933501704010017]
[133]
Zhang YJ, Gallis B, Taya M, Wang S, Ho RJY, Sasaki T. pH-responsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and induce down-regulation of HER family members. PLoS One 2013; 8(3) e59086
[http://dx.doi.org/10.1371/journal.pone.0059086] [PMID: 23516601]
[134]
Aditya NP, Patankar S, Madhusudhan B, Murthy RSR, Souto EB. Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: pharmacokinetics, toxicological and in vivo anti-malarial activity. Eur J Pharm Sci 2010; 40(5): 448-55.
[http://dx.doi.org/10.1016/j.ejps.2010.05.007] [PMID: 20493255]
[135]
Aderibigbe BA. Design of drug delivery systems containing artemisinin and its derivatives. Molecules 2017; 22(2) e323
[http://dx.doi.org/10.3390/molecules22020323] [PMID: 28230749]
[136]
Zyad A, Tilaoui M, Jaafari A, Oukerrou MA, Mouse HA. More insights into the pharmacological effects of artemisinin. Phytother Res 2018; 32(2): 216-29.
[http://dx.doi.org/10.1002/ptr.5958] [PMID: 29193409]
[137]
Gharib A, Faezizadeh Z, Mesbah-Namin SAR, Saravani R. Preparation, characterization and in vitro efficacy of magnetic nanoliposomes containing the artemisinin and transferrin. Daru 2014; 22: 44.
[http://dx.doi.org/10.1186/2008-2231-22-44] [PMID: 24887240]
[138]
Piccinino D, Capecchi E, Botta L, et al. Layer-by-layer preparation of microcapsules and nanocapsules of mixed polyphenols with high antioxidant and UV-shielding properties. Biomacromolecules 2018; 19(9): 3883-93.
[http://dx.doi.org/10.1021/acs.biomac.8b01006] [PMID: 30088918]
[139]
Rezaei B, Majidi N. Multiwalled carbon nanotubes effect on the bioavailability of artemisinin and its cytotoxity to cancerous cells. J Nanopart Res 2011; 13: 6339-46.
[http://dx.doi.org/10.1007/s11051-011-0376-1]
[140]
Europe A, Europe J, External R. Multifunctional mesoporous nanoparticles as pH responsive Fe2+reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth. Biomaterials 2014; 6498-507.
[141]
Liu K, Dai L, Li C, Liu J, Wang L, Lei J. Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol-dihydroartemisinin conjugate. Sci Rep 2016; 6: 29461.
[http://dx.doi.org/10.1038/srep29461] [PMID: 27377918]
[142]
Wang D, Li H, Gu J, et al. Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. J Pharm Biomed Anal 2013; 83: 141-8.
[http://dx.doi.org/10.1016/j.jpba.2013.05.001] [PMID: 23732534]
[143]
Sagara I, Diallo A, Kone M, et al. A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg 2008; 79(5): 655-61.
[http://dx.doi.org/10.4269/ajtmh.2008.79.655] [PMID: 18981499]
[144]
Kumari K, Keshari S, Sengupta D, Sabat SC, Mishra SK. Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment. BMC Cancer 2017; 17(1): 858.
[http://dx.doi.org/10.1186/s12885-017-3863-7] [PMID: 29246124]
[145]
Ma Y, Lu T, Zhao W, et al. Enhanced antimalarial activity by a novel artemether-lumefantrine lipid emulsion for parenteral administration. Antimicrob Agents Chemother 2014; 58(10): 5658-65.
[http://dx.doi.org/10.1128/AAC.01428-13] [PMID: 24982079]
[146]
Ilkhanizadeh B, Mehrshad A, Seddighnia A, Zarei L. Comparison between effects of free and niosomal formulations of Artemisia annua L. (asteraceae) on chronic myelogenous leukemia (K562) cell line. Int J Pharmacol 2017; 13: 191-7.
[http://dx.doi.org/10.3923/ijp.2017.191.197]
[147]
Jin M, Shen X, Zhao C, et al. In vivo study of effects of artesunate nanoliposomes on human hepatocellular carcinoma xenografts in nude mice. Drug Deliv 2013; 20(3-4): 127-33.
[http://dx.doi.org/10.3109/10717544.2013.801047] [PMID: 23731485]
[148]
Zhang H, Hou L, Jiao X, Ji Y, Zhu X, Zhang Z. Transferrin-mediated fullerenes nanoparticles as Fe(2+)-dependent drug vehicles for synergistic anti-tumor efficacy. Biomaterials 2015; 37: 353-66.
[http://dx.doi.org/10.1016/j.biomaterials.2014.10.031] [PMID: 25453964]
[149]
Wang Y, Han Y, Yang Y, et al. Effect of interaction of magnetic nanoparticles of Fe3O4 and artesunate on apoptosis of K562 cells. Int J Nanomedicine 2011; 6: 1185-92.
[PMID: 21822380]
[150]
Hou L, Block KE, Huang H. Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis. PLoS One 2014; 9(8) e104762
[http://dx.doi.org/10.1371/journal.pone.0104762] [PMID: 25116436]
[151]
Cheng C, Ho WE, Goh FY, et al. Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway. PLoS One 2011; 6(6) e20932
[http://dx.doi.org/10.1371/journal.pone.0020932] [PMID: 21695271]
[152]
Hoffmann HJ. News in cellular allergology: a review of the human mast cell and basophil granulocyte literature from January 2013 to May 2015. Int Arch Allergy Immunol 2015; 168(4): 253-62.
[http://dx.doi.org/10.1159/000443960] [PMID: 26895271]
[153]
Tan SS, Ong B, Cheng C, et al. The antimalarial drug artesunate inhibits primary human cultured airway smooth muscle cell proliferation. Am J Respir Cell Mol Biol 2014; 50(2): 451-8.
[PMID: 24066853]
[154]
Singh NP, Verma KB. Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 2002; 10: 279-80.
[http://dx.doi.org/10.2298/AOO0204279S]
[155]
Krishna S, Ganapathi S, Ster IC, et al. A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine 2014; 2(1): 82-90.
[http://dx.doi.org/10.1016/j.ebiom.2014.11.010] [PMID: 26137537]
[156]
von Hagens C, Walter-Sack I, Goeckenjan M, et al. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat 2017; 164(2): 359-69.
[http://dx.doi.org/10.1007/s10549-017-4261-1] [PMID: 28439738]
[157]
Deeken JF, Wang H, Hartley M, et al. A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol 2018; 81(3): 587-96.
[http://dx.doi.org/10.1007/s00280-018-3533-8] [PMID: 29392450]
[158]
Zhang ZY, Yu SQ, Miao LY, et al. [Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial]. J Chin Integr Med 2008; 6(2): 134-8.
[http://dx.doi.org/10.3736/jcim20080206] [PMID: 18241646]
[159]
Jansen FH, Adoubi I, J C KC, et al. First study of oral Artenimol-R in advanced cervical cancer: clinical benefit, tolerability and tumor markers. Anticancer Res 2011; 31(12): 4417-22.
[PMID: 22199309]
[160]
Mott BT, He R, Chen X, et al. Artemisinin-derived dimer phosphate esters as potent anti-cytomegalovirus (anti-CMV) and anti-cancer agents: a structure-activity study. Bioorg Med Chem 2013; 21(13): 3702-7.
[http://dx.doi.org/10.1016/j.bmc.2013.04.027] [PMID: 23673218]


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