Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy

Author(s): Shunqin Zhu, Qin Yu, Chunsong Huo, Yuanpeng Li, Linshen He, Botian Ran, Ji Chen, Yonghao Li and Wanhong Liu*

Volume 28, Issue 2, 2021

Published on: 21 January, 2020

Page: [329 - 345] Pages: 17

DOI: 10.2174/0929867327666200121124404

Price: $65

Abstract

Background: Artemisinin is a sesquiterpene lactone compound with a special peroxide bridge that is tightly linked to the cytotoxicity involved in fighting malaria and cancer. Artemisinin and its derivatives (ARTs) are considered to be potential anticancer drugs that promote cancer cell apoptosis, induce cell cycle arrest and autophagy, inhibit cancer cell invasion and migration. Additionally, ARTs significantly increase intracellular Reactive Oxygen Species (ROS) in cancer cells, which result in ferroptosis, a new form of cell death, depending on the ferritin concentration. Ferroptosis is regarded as a cancer suppressor and as well as considered a new mechanism for cancer therapy.

Methods: The anticancer activities of ARTs and reference molecules were compared by literature search and analysis. The latest research progress on ferroptosis was described, with a special focus on the molecular mechanism of artemisinin-induced ferroptosis.

Results: Artemisinin derivatives, artemisinin-derived dimers, hybrids and artemisinin-transferrin conjugates, could significantly improve anticancer activity, and their IC50 values are lower than those of reference molecules such as doxorubicin and paclitaxel. The biological activities of linkers in dimers and hybrids are important in the drug design processes. ARTs induce ferroptosis mainly by triggering intracellular ROS production, promoting the lysosomal degradation of ferritin and regulating the System Xc-/Gpx4 axis. Interestingly, ARTs also stimulate the feedback inhibition pathway.

Conclusion: Artemisinin and its derivatives could be used in the future as cancer therapies with broader applications due to their induction of ferroptosis. Meanwhile, more attention should be paid to the development of novel artemisinin-related drugs based on the mechanism of artemisinininduced ferroptosis.

Keywords: Artemisinin derivatives, drug design, ferroptosis, cancer, system Xc-/Gpx4 axis, molecular mechanism.

[1]
Crespo-Ortiz, M.P.; Wei, M.Q. 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]
[2]
Lai, H.C.; Singh, N.P.; Sasaki, T. Development of artemisinin compounds for cancer treatment. Invest. New Drugs, 2013, 31(1), 230-246.
[http://dx.doi.org/10.1007/s10637-012-9873-z] [PMID: 22935909]
[3]
Muregi, F.W.; Ishih, A. Next‐generation antimalarial drugs: hybrid molecules as a new strategy in drug design. Drug Dev. Res., 2010, 71(1), 20-32.
[http://dx.doi.org/10.1002/ddr.20345] [PMID: 21399701]
[4]
Zhang, C.J.; Wang, J.; Zhang, J.; Lee, Y.M.; Feng, G.; Lim, T.K.; Shen, H.M.; Lin, Q.; Liu, B. Mechanism-Guided Design and Synthesis of a Mitochondria-Targeting Artemisinin Analogue with Enhanced Anticancer Activity. Angew. Chem. Int. Ed. Engl., 2016, 55(44), 13770-13774.
[http://dx.doi.org/10.1002/anie.201607303] [PMID: 27709833]
[5]
Kung, S.H.; Lund, S.; Murarka, A.; McPhee, D.; Paddon, C.J. Approaches and Recent Developments for the Commercial Production of Semi-synthetic Artemisinin. Front. Plant Sci., 2018, 9, 87.
[http://dx.doi.org/10.3389/fpls.2018.00087] [PMID: 29445390]
[6]
Lu, Y.Y.; Chen, T.S.; Qu, J.L.; Pan, W.L.; Sun, L.; Wei, X.B. Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J. Biomed. Sci., 2009, 16(1), 16.
[http://dx.doi.org/10.1186/1423-0127-16-16] [PMID: 19272183]
[7]
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), 5519-5530.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0197] [PMID: 18765544]
[8]
Våtsveen, T.K.; Myhre, M.R.; Steen, C.B.; Wälchli, S.; Lingjærde, O.C.; Bai, B.; Dillard, P.; Theodossiou, T.A.; Holien, T.; Sundan, A.; Inderberg, E.M.; Smeland, E.B.; Myklebust, J.H.; Oksvold, M.P. Artesunate shows potent anti-tumor activity in B-cell lymphoma. J. Hematol. Oncol., 2018, 11(1), 23.
[http://dx.doi.org/10.1186/s13045-018-0561-0] [PMID: 29458389]
[9]
Zhu, S.; Liu, W.; Ke, X.; Li, J.; Hu, R.; Cui, H.; Song, G. Artemisinin reduces cell proliferation and induces apoptosis in neuroblastoma. Oncol. Rep., 2014, 32(3), 1094-1100.
[http://dx.doi.org/10.3892/or.2014.3323] [PMID: 25017372]
[10]
Willoughby, J.A., Sr; Sundar, S.N.; Cheung, M.; Tin, A.S.; Modiano, J.; Firestone, G.L. Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J. Biol. Chem., 2009, 284(4), 2203-2213.
[http://dx.doi.org/10.1074/jbc.M804491200] [PMID: 19017637]
[11]
Chen, H.; Sun, B.; Wang, S.; Pan, S.; Gao, Y.; Bai, X.; Xue, D. Growth inhibitory effects of dihydroartemisinin on pancreatic cancer cells: involvement of cell cycle arrest and inactivation of nuclear factor-kappaB. J. Cancer Res. Clin. Oncol., 2010, 136(6), 897-903.
[http://dx.doi.org/10.1007/s00432-009-0731-0] [PMID: 19941148]
[12]
Du, X.X.; Li, Y.J.; Wu, C.L.; Zhou, J.H.; Han, Y.; Sui, H.; Wei, X.L.; Liu, L.; Huang, P.; Yuan, H.H.; Zhang, T.T.; Zhang, W.J.; Xie, R.; Lang, X.H.; Jia, D.X.; Bai, Y.X. Initiation of apoptosis, cell cycle arrest and autophagy of esophageal cancer cells by dihydroartemisinin. Biomed. Pharmacother., 2013, 67(5), 417-424.
[http://dx.doi.org/10.1016/j.biopha.2013.01.013] [PMID: 23582790]
[13]
Liu, X.; Wu, J.; Fan, M.; Shen, C.; Dai, W.; Bao, Y.; Liu, J.H.; Yu, B.Y. Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells. Cell Death Dis., 2018, 9(11), 1048.
[http://dx.doi.org/10.1038/s41419-018-1006-y] [PMID: 30323180]
[14]
Yao, G.D.; Ge, M.Y.; Li, D.Q.; Chen, L.; Hayashi, T.; Tashiro, S.I.; Onodera, S.; Guo, C.; Song, S.J.; Ikejima, T. L-A03, a dihydroartemisinin derivative, promotes apoptotic cell death of human breast cancer MCF-7 cells by targeting c-Jun N-terminal kinase. Biomed. Pharmacother., 2018, 105, 320-325.
[http://dx.doi.org/10.1016/j.biopha.2018.05.093] [PMID: 29864620]
[15]
Jiang, L.B.; Meng, D.H.; Lee, S.M.; Liu, S.H.; Xu, Q.T.; Wang, Y.; Zhang, J. Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway. Sci. Rep., 2016, 6(1), 38979.
[http://dx.doi.org/10.1038/srep38979] [PMID: 27941926]
[16]
Hu, W.; Chen, S.S.; Zhang, J.L.; Lou, X.E.; Zhou, H.J. Dihydroartemisinin induces autophagy by suppressing NF-κB activation. Cancer Lett., 2014, 343(2), 239-248.
[http://dx.doi.org/10.1016/j.canlet.2013.09.035] [PMID: 24099910]
[17]
Que, Z.; Wang, P.; Hu, Y.; Xue, Y.; Liu, X.; Qu, C.; Ma, J.; Liu, Y. Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling. Pharmacol. Res., 2017, 119, 72-88.
[http://dx.doi.org/10.1016/j.phrs.2017.01.014] [PMID: 28111262]
[18]
Lian, S.; Shi, R.; Huang, X.; Hu, X.; Song, B.; Bai, Y.; Yang, B.; Dong, J.; Du, Z.; Zhang, Y.; Jia, J.; Ma, N.; Guo, G.; Wang, M. Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties. Oncol. Rep., 2016, 36(2), 984-990.
[http://dx.doi.org/10.3892/or.2016.4847] [PMID: 27279152]
[19]
Zhang, F.; Ma, Q.; Xu, Z.; Liang, H.; Li, H.; Ye, Y.; Xiang, S.; Zhang, Y.; Jiang, L.; Hu, Y.; Wang, Z.; Wang, X.; Zhang, Y.; Gong, W.; Liu, Y. Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer. J. Exp. Clin. Cancer Res., 2017, 36(1), 68.
[http://dx.doi.org/10.1186/s13046-017-0531-3] [PMID: 28506239]
[20]
Efferth, T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin. Cancer Biol., 2017, 46, 65-83.
[http://dx.doi.org/10.1016/j.semcancer.2017.02.009] [PMID: 28254675]
[21]
Wong, Y.K.; Xu, C.; Kalesh, K.A.; He, Y.; Lin, Q.; Wong, W.S.F.; Shen, H.M.; Wang, J. Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action. Med. Res. Rev., 2017, 37(6), 1492-1517.
[http://dx.doi.org/10.1002/med.21446] [PMID: 28643446]
[22]
Ho, W.E.; Peh, H.Y.; Chan, T.K.; Wong, W.S. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol. Ther., 2014, 142(1), 126-139.
[http://dx.doi.org/10.1016/j.pharmthera.2013.12.001] [PMID: 24316259]
[23]
Stockwell, B.R.; Friedmann Angeli, J.P.; Bayir, H.; Bush, A.I.; Conrad, M.; Dixon, S.J.; Fulda, S.; Gascón, S.; Hatzios, S.K.; Kagan, V.E.; Noel, K.; Jiang, X.; Linkermann, A.; Murphy, M.E.; Overholtzer, M.; Oyagi, A.; Pagnussat, G.C.; Park, J.; Ran, Q.; Rosenfeld, C.S.; Salnikow, K.; Tang, D.; Torti, F.M.; Torti, S.V.; Toyokuni, S.; Woerpel, K.A.; Zhang, D.D. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 2017, 171(2), 273-285.
[http://dx.doi.org/10.1016/j.cell.2017.09.021] [PMID: 28985560]
[24]
Ooko, E.; Saeed, M.E.; Kadioglu, O.; Sarvi, S.; Colak, M.; Elmasaoudi, K.; Janah, R.; Greten, H.J.; Efferth, T. Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells. Phytomedicine, 2015, 22(11), 1045-1054.
[http://dx.doi.org/10.1016/j.phymed.2015.08.002] [PMID: 26407947]
[25]
Zhang, S.; Gerhard, G.S. Heme mediates cytotoxicity from artemisinin and serves as a general anti-proliferation target. PLoS One, 2009, 4(10)e7472
[http://dx.doi.org/10.1371/journal.pone.0007472] [PMID: 19862332]
[26]
Aderibigbe, B.A. Design of drug delivery systems containing artemisinin and its derivatives. Molecules, 2017, 22(2), 323.
[http://dx.doi.org/10.3390/molecules22020323] [PMID: 28230749]
[27]
Zyad, A.; Tilaoui, M.; Jaafari, A.; Oukerrou, M.A.; Mouse, H.A. More insights into the pharmacological effects of artemisinin. Phytother. Res., 2018, 32(2), 216-229.
[http://dx.doi.org/10.1002/ptr.5958] [PMID: 29193409]
[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), 303-319.
[http://dx.doi.org/10.1007/s13659-018-0162-1] [PMID: 29633188]
[29]
Singh, N.; Verma, K. Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch. Oncol., 2002, 10(4), 279-280.
[http://dx.doi.org/10.2298/AOO0204279S]
[30]
Berger, T.G.; Dieckmann, D.; Efferth, T.; Schultz, E.S.; Funk, J.O.; Baur, A.; Schuler, G. Artesunate in the treatment of metastatic uveal melanoma--first experiences. Oncol. Rep., 2005, 14(6), 1599-1603.
[http://dx.doi.org/10.3892/or.14.6.1599] [PMID: 16273263]
[31]
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), 451-466.
[http://dx.doi.org/10.1007/s00280-017-3251-7] [PMID: 28210763]
[32]
Konstat-Korzenny, E.; Ascencio-Aragón, J.A.; Niezen-Lugo, S.; Vázquez-López, R. Artemisinin and its synthetic derivatives as a possible therapy for cancer. Med. Sci. (Basel), 2018, 6(1), 19.
[http://dx.doi.org/10.3390/medsci6010019] [PMID: 29495461]
[33]
Chow, L.M.; Chan, T.H. Novel classes of dimer antitumour drug candidates. Curr. Pharm. Des., 2009, 15(6), 659-674.
[http://dx.doi.org/10.2174/138161209787315576] [PMID: 19199989]
[34]
Posner, G.H.; Ploypradith, P.; Parker, M.H.; O’Dowd, H.; Woo, S.H.; Northrop, J.; Krasavin, M.; Dolan, P.; Kensler, T.W.; Xie, S.; Shapiro, T.A. Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. J. Med. Chem., 1999, 42(21), 4275-4280.
[http://dx.doi.org/10.1021/jm990363d] [PMID: 10543871]
[35]
Posner, G.H.; D’Angelo, J.M.; O’Neill, P.; Mercer, A. Anticancer activity of artemisinin-derived trioxanes. Expert Opin. Ther. Pat., 2006, 16(12), 1665-1672.
[http://dx.doi.org/10.1517/13543776.16.12.1665]
[36]
Mott, B.T.; He, R.; Chen, X.; Fox, J.M.; Civin, C.I.; Arav-Boger, R.; Posner, G.H. 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), 3702-3707.
[http://dx.doi.org/10.1016/j.bmc.2013.04.027] [PMID: 23673218]
[37]
Slade, D.; Galal, A.M.; Gul, W.; Radwan, M.M.; Ahmed, S.A.; Khan, S.I.; Tekwani, B.L.; Jacob, M.R.; Ross, S.A.; Elsohly, M.A. Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers. Bioorg. Med. Chem., 2009, 17(23), 7949-7957.
[http://dx.doi.org/10.1016/j.bmc.2009.10.019] [PMID: 19879765]
[38]
Galal, A.M.; Gul, W.; Slade, D.; Ross, S.A.; Feng, S.; Hollingshead, M.G.; Alley, M.C.; Kaur, G.; ElSohly, M.A. Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity. Bioorg. Med. Chem., 2009, 17(2), 741-751.
[http://dx.doi.org/10.1016/j.bmc.2008.11.050] [PMID: 19084416]
[39]
Reiter, C.; Fröhlich, T.; Gruber, L.; Hutterer, C.; Marschall, M.; Voigtländer, C.; Friedrich, O.; Kappes, B.; Efferth, T.; Tsogoeva, S.B. Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities. Bioorg. Med. Chem., 2015, 23(17), 5452-5458.
[http://dx.doi.org/10.1016/j.bmc.2015.07.048] [PMID: 26260339]
[40]
Wang, S.; Sasaki, T. Synthesis of artemisinin dimers using the Ugi reaction and their in vitro efficacy on breast cancer cells. Bioorg. Med. Chem. Lett., 2013, 23(15), 4424-4427.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.057] [PMID: 23790541]
[41]
Alagbala, A.A.; McRiner, A.J.; Borstnik, K.; Labonte, T.; Chang, W.; D’Angelo, J.G.; Posner, G.H.; Foster, B.A. Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in prostate cancer cell lines. J. Med. Chem., 2006, 49(26), 7836-7842.
[http://dx.doi.org/10.1021/jm060803i] [PMID: 17181166]
[42]
Stockwin, L.H.; Han, B.; Yu, S.X.; Hollingshead, M.G.; ElSohly, M.A.; Gul, W.; Slade, D.; Galal, A.M.; Newton, D.L.; Bumke, M.A. Artemisinin dimer anticancer activity correlates with heme-catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction. Int. J. Cancer, 2009, 125(6), 1266-1275.
[http://dx.doi.org/10.1002/ijc.24496] [PMID: 19533749]
[43]
Beekman, A.C.; Barentsen, A.R.; Woerdenbag, H.J.; Van Uden, W.; Pras, N.; Konings, A.W.; el-Feraly, F.S.; Galal, A.M.; Wikström, H.V. Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J. Nat. Prod., 1997, 60(4), 325-330.
[http://dx.doi.org/10.1021/np9605495] [PMID: 9134741]
[44]
Posner, G.H.; McRiner, A.J.; Paik, I.H.; Sur, S.; Borstnik, K.; Xie, S.; Shapiro, T.A.; Alagbala, A.; Foster, B. Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane dimers in rodents. J. Med. Chem., 2004, 47(5), 1299-1301.
[http://dx.doi.org/10.1021/jm0303711] [PMID: 14971910]
[45]
Paik, I.H.; Xie, S.; Shapiro, T.A.; Labonte, T.; Narducci Sarjeant, A.A.; Baege, A.C.; Posner, G.H. Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activity. J. Med. Chem., 2006, 49(9), 2731-2734.
[http://dx.doi.org/10.1021/jm058288w] [PMID: 16640333]
[46]
Lombard, M.C.; N’Da, D.D.; Breytenbach, J.C.; Kolesnikova, N.I.; Tran Van Ba, C.; Wein, S.; Norman, J.; Denti, P.; Vial, H.; Wiesner, L. Antimalarial and anticancer activities of artemisinin-quinoline hybrid-dimers and pharmacokinetic properties in mice. Eur. J. Pharm. Sci., 2012, 47(5), 834-841.
[http://dx.doi.org/10.1016/j.ejps.2012.09.019] [PMID: 23069618]
[47]
He, R.; Mott, B.T.; Rosenthal, A.S.; Genna, D.T.; Posner, G.H.; Arav-Boger, R. An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV) and anti-cancer activities. PLoS One, 2011, 6(8)e24334
[http://dx.doi.org/10.1371/journal.pone.0024334] [PMID: 21904628]
[48]
Buragohain, P.; Saikia, B.; Surineni, N.; Barua, N.C.; Saxena, A.K.; Suri, N. Synthesis of a novel series of artemisinin dimers with potent anticancer activity involving Sonogashira cross-coupling reaction. Bioorg. Med. Chem. Lett., 2014, 24(1), 237-239.
[http://dx.doi.org/10.1016/j.bmcl.2013.11.032] [PMID: 24332623]
[49]
Pinheiro, L.C.S.; Feitosa, L.M.; Silveira, F.F.D.; Boechat, N. Current antimalarial therapies and advances in the development of semi-synthetic artemisinin derivatives. An. Acad. Bras. Cienc., 2018, 90(1)(Suppl. 2), 1251-1271.
[http://dx.doi.org/10.1590/0001-3765201820170830] [PMID: 29873667]
[50]
Fortin, S.; Bérubé, G. Advances in the development of hybrid anticancer drugs. Expert Opin. Drug Discov., 2013, 8(8), 1029-1047.
[http://dx.doi.org/10.1517/17460441.2013.798296] [PMID: 23646979]
[51]
Mercer, A.E.; Maggs, J.L.; Sun, X.M.; Cohen, G.M.; Chadwick, J.; O’Neill, P.M.; Park, B.K. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J. Biol. Chem., 2007, 282(13), 9372-9382.
[http://dx.doi.org/10.1074/jbc.M610375200] [PMID: 17227762]
[52]
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), 1331.
[http://dx.doi.org/10.3390/molecules21101331] [PMID: 27739410]
[53]
Jones, M.; Mercer, A.E.; Stocks, P.A.; La Pensée, L.J.; Cosstick, R.; Park, B.K.; Kennedy, M.E.; Piantanida, I.; Ward, S.A.; Davies, J.; Bray, P.G.; Rawe, S.L.; Baird, J.; Charidza, T.; Janneh, O.; O’Neill, P.M. Antitumour and antimalarial activity of artemisinin-acridine hybrids. Bioorg. Med. Chem. Lett., 2009, 19(7), 2033-2037.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.028] [PMID: 19249201]
[54]
Zi, C.T.; Yang, L.; Xu, F.Q.; Dong, F.W.; Yang, D.; Li, Y.; Ding, Z.T.; Zhou, J.; Jiang, Z.H.; Hu, J.M. Synthesis and anticancer activity of dimeric podophyllotoxin derivatives. Drug Des. Devel. Ther., 2018, 12, 3393-3406.
[http://dx.doi.org/10.2147/DDDT.S167382] [PMID: 30349193]
[55]
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]
[56]
Ha, V.T.; Kien, V.T.; Binh, H.; Tien, V.D.; My, N.T.; Nam, N.H.; Baltas, M.; Hahn, H.; Han, B.W.; Thao, T.; Vu, T.K. Design, synthesis and biological evaluation of novel hydroxamic acids bearing artemisinin skeleton. Bioorg. Chem., 2016, 66, 63-71.
[http://dx.doi.org/10.1016/j.bioorg.2016.03.008] [PMID: 27018835]
[57]
La Pensée, L. Sabbani, S.; Sharma, R.; Bhamra, I.; Shore, E.; Chadwick, A.E.; Berry, N.G.; Firman, J.; Araujo, N.C.; Cabral, L.; Cristiano, M.L.; Bateman, C.; Janneh, O.; Gavrila, A.; Wu, Y.H.; Hussain, A.; Ward, S.A.; Stocks, P.A.; Cosstick, R.; O’Neill, P.M. Artemisinin-polypyrrole conjugates: synthesis, DNA binding studies and preliminary antiproliferative evaluation. ChemMedChem, 2013, 8(5), 709-718.
[http://dx.doi.org/10.1002/cmdc.201200536] [PMID: 23495190]
[58]
Xie, L.; Zhai, X.; Liu, C.; Li, P.; Li, Y.; Guo, G.; Gong, P. Anti-tumor activity of new artemisinin-chalcone hybrids. Arch. Pharm. (Weinheim), 2011, 344(10), 639-647.
[http://dx.doi.org/10.1002/ardp.201000391] [PMID: 21984014]
[59]
Wang, L.; Świtalska, M.; Wang, N.; Du, Z.J.; Fukumoto, Y.; Diep, N.K.; Kiguchi, R.; Nokami, J.; Wietrzyk, J.; Inokuchi, T. Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents. Molecules, 2014, 19(11), 19021-19035.
[http://dx.doi.org/10.3390/molecules191119021] [PMID: 25412047]
[60]
Fröhlich, T.; Ndreshkjana, B.; Muenzner, J.K.; Reiter, C.; Hofmeister, E.; Mederer, S.; Fatfat, M.; El-Baba, C.; Gali-Muhtasib, H.; Schneider-Stock, R.; Tsogoeva, S.B. Synthesis of Novel Hybrids of Thymoquinone and Artemisinin with High Activity and Selectivity Against Colon Cancer. ChemMedChem, 2017, 12(3), 226-234.
[http://dx.doi.org/10.1002/cmdc.201600594] [PMID: 27973725]
[61]
Letis, A.S.; Seo, E.J.; Nikolaropoulos, S.S.; Efferth, T.; Giannis, A.; Fousteris, M.A. Synthesis and cytotoxic activity of new artemisinin hybrid molecules against human leukemia cells. Bioorg. Med. Chem., 2017, 25(13), 3357-3367.
[http://dx.doi.org/10.1016/j.bmc.2017.04.021] [PMID: 28456567]
[62]
Ma, G.T.; Lee, S.K.; Park, K.K.; Park, J.; Son, S.H.; Jung, M.; Chung, W.Y. Artemisinin-Daumone Hybrid Inhibits Cancer Cell-Mediated Osteolysis by Targeting Cancer Cells and Osteoclasts. Cell. Physiol. Biochem., 2018, 49(4), 1460-1475.
[http://dx.doi.org/10.1159/000493449] [PMID: 30205376]
[63]
Yu, H.; Hou, Z.; Tian, Y.; Mou, Y.; Guo, C. Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents. Eur. J. Med. Chem., 2018, 151, 434-449.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.005] [PMID: 29649740]
[64]
Lai, H.; Singh, N.P. Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett., 1995, 91(1), 41-46.
[http://dx.doi.org/10.1016/0304-3835(94)03716-V] [PMID: 7750093]
[65]
Singh, N.P.; Lai, H. Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci., 2001, 70(1), 49-56.
[http://dx.doi.org/10.1016/S0024-3205(01)01372-8] [PMID: 11764006]
[66]
Nakase, I.; Gallis, B.; Takatani-Nakase, T.; Oh, S.; Lacoste, E.; Singh, N.P.; Goodlett, D.R.; Tanaka, S.; Futaki, S.; Lai, H.; Sasaki, T. Transferrin receptor-dependent cytotoxicity of artemisinin-transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer Lett., 2009, 274(2), 290-298.
[http://dx.doi.org/10.1016/j.canlet.2008.09.023] [PMID: 19006645]
[67]
Lai, H.; Nakase, I.; Lacoste, E.; Singh, N.P.; Sasaki, T. Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res., 2009, 29(10), 3807-3810.
[PMID: 19846912]
[68]
Nakase, I.; Lai, H.; Singh, N.P.; Sasaki, T. Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int. J. Pharm., 2008, 354(1-2), 28-33.
[http://dx.doi.org/10.1016/j.ijpharm.2007.09.003] [PMID: 17942255]
[69]
Gatter, K.C.; Brown, G.; Trowbridge, I.S.; Woolston, R.E.; Mason, D.Y. Transferrin receptors in human tissues: their distribution and possible clinical relevance. J. Clin. Pathol., 1983, 36(5), 539-545.
[http://dx.doi.org/10.1136/jcp.36.5.539] [PMID: 6302135]
[70]
Efferth, T.; Benakis, A.; Romero, M.R.; Tomicic, M.; Rauh, R.; Steinbach, D.; Häfer, R.; Stamminger, T.; Oesch, F.; Kaina, B.; Marschall, M. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic. Biol. Med., 2004, 37(7), 998-1009.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.023] [PMID: 15336316]
[71]
Gong, Y.; Gallis, B.M.; Goodlett, D.R.; Yang, Y.; Lu, H.; Lacoste, E.; Lai, H.; Sasaki, T. Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines. Anticancer Res., 2013, 33(1), 123-132.
[PMID: 23267137]
[72]
Du, S.; Xu, G.; Zou, W.; Xiang, T.; Luo, Z. Effect of dihydroartemisinin on UHRF1 gene expression in human prostate cancer PC-3 cells. Anticancer Drugs, 2017, 28(4), 384-391.
[http://dx.doi.org/10.1097/CAD.0000000000000469] [PMID: 28059831]
[73]
Wu, B.; Hu, K.; Li, S.; Zhu, J.; Gu, L.; Shen, H.; Hambly, B.D.; Bao, S.; Di, W. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer. Oncol. Rep., 2012, 27(1), 101-108.
[http://dx.doi.org/10.3892/or.2011.1505] [PMID: 22025319]
[74]
Zhou, H.J.; Wang, W.Q.; Wu, G.D.; Lee, J.; Li, A. Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. Vascul. Pharmacol., 2007, 47(2-3), 131-138.
[http://dx.doi.org/10.1016/j.vph.2007.05.002] [PMID: 17581794]
[75]
Jia, J.; Qin, Y.; Zhang, L.; Guo, C.; Wang, Y.; Yue, X.; Qian, J. Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis. Mol. Med. Rep., 2016, 13(5), 4461-4468.
[http://dx.doi.org/10.3892/mmr.2016.5073] [PMID: 27035431]
[76]
Liao, K.; Li, J.; Wang, Z. Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells. Int. J. Clin. Exp. Pathol., 2014, 7(12), 8684-8691.[doi].
[PMID: 25674233]
[77]
Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; Morrison, B., III; Stockwell, B.R. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5), 1060-1072.
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[78]
Yu, H.; Guo, P.; Xie, X.; Wang, Y.; Chen, G. Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J. Cell. Mol. Med., 2017, 21(4), 648-657.
[http://dx.doi.org/10.1111/jcmm.13008] [PMID: 27860262]
[79]
Friedmann Angeli, J.P.; Schneider, M.; Proneth, B.; Tyurina, Y.Y.; Tyurin, V.A.; Hammond, V.J.; Herbach, N.; Aichler, M.; Walch, A.; Eggenhofer, E.; Basavarajappa, D.; Rådmark, O.; Kobayashi, S.; Seibt, T.; Beck, H.; Neff, F.; Esposito, I.; Wanke, R.; Förster, H.; Yefremova, O.; Heinrichmeyer, M.; Bornkamm, G.W.; Geissler, E.K.; Thomas, S.B.; Stockwell, B.R.; O’Donnell, V.B.; Kagan, V.E.; Schick, J.A.; Conrad, M. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol., 2014, 16(12), 1180-1191.
[http://dx.doi.org/10.1038/ncb3064] [PMID: 25402683]
[80]
Gao, M.; Monian, P.; Quadri, N.; Ramasamy, R.; Jiang, X. Glutaminolysis and Transferrin Regulate Ferroptosis. Mol. Cell, 2015, 59(2), 298-308.
[http://dx.doi.org/10.1016/j.molcel.2015.06.011] [PMID: 26166707]
[81]
Yang, W.S. SriRamaratnam, R.; Welsch, M.E.; Shimada, K.; Skouta, R.; Viswanathan, V.S.; Cheah, J.H.; Clemons, P.A.; Shamji, A.F.; Clish, C.B.; Brown, L.M.; Girotti, A.W.; Cornish, V.W.; Schreiber, S.L.; Stockwell, B.R. Regulation of ferroptotic cancer cell death by GPX4. Cell, 2014, 156(1-2), 317-331.
[http://dx.doi.org/10.1016/j.cell.2013.12.010] [PMID: 24439385]
[82]
Gout, P.W.; Simms, C.R.; Robertson, M.C. In vitro studies on the lymphoma growth-inhibitory activity of sulfasalazine. Anticancer Drugs, 2003, 14(1), 21-29.
[http://dx.doi.org/10.1097/00001813-200301000-00004] [PMID: 12544255]
[83]
Dongiovanni, P.; Valenti, L.; Ludovica Fracanzani, A.; Gatti, S.; Cairo, G.; Fargion, S. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am. J. Pathol., 2008, 172(3), 738-747.
[http://dx.doi.org/10.2353/ajpath.2008.070097] [PMID: 18245813]
[84]
Roh, J.L.; Kim, E.H.; 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, 254-262.
[http://dx.doi.org/10.1016/j.redox.2016.12.010] [PMID: 28012440]
[85]
Eling, N.; Reuter, L.; Hazin, J.; Hamacher-Brady, A.; Brady, N.R. Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience, 2015, 2(5), 517-532.
[http://dx.doi.org/10.18632/oncoscience.160] [PMID: 26097885]
[86]
Greenshields, A.L.; Shepherd, T.G.; Hoskin, D.W. Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Mol. Carcinog., 2017, 56(1), 75-93.
[http://dx.doi.org/10.1002/mc.22474] [PMID: 26878598]
[87]
Chen, L.; Li, X.; Liu, L.; Yu, B.; Xue, Y.; Liu, Y. Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-γ-lyase function. Oncol. Rep., 2015, 33(3), 1465-1474.
[http://dx.doi.org/10.3892/or.2015.3712] [PMID: 25585997]
[88]
Yamaguchi, H.; Hsu, J.L.; Chen, C.T.; Wang, Y.N.; Hsu, M.C.; Chang, S.S.; Du, Y.; Ko, H.W.; Herbst, R.; Hung, M.C. Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin. Cancer Res., 2013, 19(4), 845-854.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2621] [PMID: 23344263]
[89]
Beguin, Y.; Aapro, M.; Ludwig, H.; Mizzen, L.; Osterborg, A. Epidemiological and nonclinical studies investigating effects of iron in carcinogenesis--a critical review. Crit. Rev. Oncol. Hematol., 2014, 89(1), 1-15.
[http://dx.doi.org/10.1016/j.critrevonc.2013.10.008] [PMID: 24275533]
[90]
Ohgami, R.S.; Campagna, D.R.; Greer, E.L.; Antiochos, B.; McDonald, A.; Chen, J.; Sharp, J.J.; Fujiwara, Y.; Barker, J.E.; Fleming, M.D. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat. Genet., 2005, 37(11), 1264-1269.
[http://dx.doi.org/10.1038/ng1658] [PMID: 16227996]
[91]
Hubert, N.; Hentze, M.W. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12345-12350.
[http://dx.doi.org/10.1073/pnas.192423399] [PMID: 12209011]
[92]
Torti, S.V.; Torti, F.M. Iron and cancer: more ore to be mined. Nat. Rev. Cancer, 2013, 13(5), 342-355.
[http://dx.doi.org/10.1038/nrc3495] [PMID: 23594855]
[93]
Bogdan, A.R.; Miyazawa, M.; Hashimoto, K.; Tsuji, Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem. Sci., 2016, 41(3), 274-286.
[http://dx.doi.org/10.1016/j.tibs.2015.11.012] [PMID: 26725301]
[94]
Kakhlon, O.; Cabantchik, Z.I. The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic. Biol. Med., 2002, 33(8), 1037-1046.
[http://dx.doi.org/10.1016/S0891-5849(02)01006-7] [PMID: 12374615]
[95]
Kruszewski, M. Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat. Res., 2003, 531(1-2), 81-92.
[http://dx.doi.org/10.1016/j.mrfmmm.2003.08.004] [PMID: 14637247]
[96]
Dixon, S.J.; Stockwell, B.R. The role of iron and reactive oxygen species in cell death. Nat. Chem. Biol., 2014, 10(1), 9-17.
[http://dx.doi.org/10.1038/nchembio.1416] [PMID: 24346035]
[97]
Mai, T.T.; Hamaï, A.; Hienzsch, A.; Cañeque, T.; Müller, S.; Wicinski, J.; Cabaud, O.; Leroy, C.; David, A.; Acevedo, V.; Ryo, A.; Ginestier, C.; Birnbaum, D.; Charafe-Jauffret, E.; Codogno, P.; Mehrpour, M.; Rodriguez, R. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat. Chem., 2017, 9(10), 1025-1033.
[http://dx.doi.org/10.1038/nchem.2778] [PMID: 28937680]
[98]
Dodson, M.; Castro-Portuguez, R.; Zhang, D.D. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol., 2019, •••23101107
[http://dx.doi.org/10.1016/j.redox.2019.101107] [PMID: 30692038]
[99]
Sun, X.; Ou, Z.; Chen, R.; Niu, X.; Chen, D.; Kang, R.; Tang, D. Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology, 2016, 63(1), 173-184.
[http://dx.doi.org/10.1002/hep.28251] [PMID: 26403645]
[100]
Harada, N.; Kanayama, M.; Maruyama, A.; Yoshida, A.; Tazumi, K.; Hosoya, T.; Mimura, J.; Toki, T.; Maher, J.M.; Yamamoto, M.; Itoh, K. Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages. Arch. Biochem. Biophys., 2011, 508(1), 101-109.
[http://dx.doi.org/10.1016/j.abb.2011.02.001] [PMID: 21303654]
[101]
Sun, X.; Ou, Z.; Xie, M.; Kang, R.; Fan, Y.; Niu, X.; Wang, H.; Cao, L.; Tang, D. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene, 2015, 34(45), 5617-5625.
[http://dx.doi.org/10.1038/onc.2015.32] [PMID: 25728673]
[102]
Mou, Y.; Wang, J.; Wu, J.; He, D.; Zhang, C.; Duan, C.; Li, B. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J. Hematol. Oncol., 2019, 12(1), 34.
[http://dx.doi.org/10.1186/s13045-019-0720-y] [PMID: 30925886]
[103]
Dixon, S.J.; Patel, D.N.; Welsch, M.; Skouta, R.; Lee, E.D.; Hayano, M.; Thomas, A.G.; Gleason, C.E.; Tatonetti, N.P.; Slusher, B.S.; Stockwell, B.R. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 2014.3e02523.
[http://dx.doi.org/10.7554/eLife.02523] [PMID: 24844246]
[104]
Feng, H.; Stockwell, B.R. Unsolved mysteries: How does lipid peroxidation cause ferroptosis? PLoS Biol., 2018, 16(5)e2006203
[http://dx.doi.org/10.1371/journal.pbio.2006203] [PMID: 29795546]
[105]
Louandre, C.; Marcq, I.; Bouhlal, H.; Lachaier, E.; Godin, C.; Saidak, Z.; François, C.; Chatelain, D.; Debuysscher, V.; Barbare, J.C.; Chauffert, B.; Galmiche, A. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells. Cancer Lett., 2015, 356(2 Pt B), 971-977.
[http://dx.doi.org/10.1016/j.canlet.2014.11.014] [PMID: 25444922]
[106]
Yu, H.; Yang, C.; Jian, L.; Guo, S.; Chen, R.; Li, K.; Qu, F.; Tao, K.; Fu, Y.; Luo, F.; Liu, S. Sulfasalazineinduced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol. Rep., 2019, 42(2), 826-838.
[http://dx.doi.org/10.3892/or.2019.7189] [PMID: 31173262]
[107]
Wang, L.; Liu, Y.; Du, T.; Yang, H.; Lei, L.; Guo, M.; Ding, H.F.; Zhang, J.; Wang, H.; Chen, X.; Yan, C. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc. Cell Death Differ., 2020, 27(2), 662-675.
[http://dx.doi.org/10.1038/s41418-019-0380-z] [PMID: 31273299]
[108]
Kang, R.; Zhu, S.; Zeh, H.J.; Klionsky, D.J.; Tang, D. BECN1 is a new driver of ferroptosis. Autophagy, 2018, 14(12), 2173-2175.
[http://dx.doi.org/10.1080/15548627.2018.1513758] [PMID: 30145930]
[109]
Jiang, L.; Kon, N.; Li, T.; Wang, S.J.; Su, T.; Hibshoosh, H.; Baer, R.; Gu, W. Ferroptosis as a p53-mediated activity during tumour suppression. Nature, 2015, 520(7545), 57-62.
[http://dx.doi.org/10.1038/nature14344] [PMID: 25799988]
[110]
Cozza, G.; Rossetto, M.; Bosello-Travain, V.; Maiorino, M.; Roveri, A.; Toppo, S.; Zaccarin, M.; Zennaro, L.; Ursini, F. Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center. Free Radic. Biol. Med., 2017, 112, 1-11.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.07.010] [PMID: 28709976]
[111]
Yang, W.S.; Stockwell, B.R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol., 2008, 15(3), 234-245.
[http://dx.doi.org/10.1016/j.chembiol.2008.02.010] [PMID: 18355723]
[112]
Ingold, I.; Berndt, C.; Schmitt, S.; Doll, S.; Poschmann, G.; Buday, K.; Roveri, A.; Peng, X.; Porto Freitas, F.; Seibt, T.; Mehr, L.; Aichler, M.; Walch, A.; Lamp, D.; Jastroch, M.; Miyamoto, S.; Wurst, W.; Ursini, F.; Arnér, E.S.J.; Fradejas-Villar, N.; Schweizer, U.; Zischka, H.; Friedmann Angeli, J.P.; Conrad, M. Selenium utilization by GPX4 Is required to prevent hydroperoxide-induced ferroptosis. Cell, 2018, 172(3), 409-422.e21.
[http://dx.doi.org/10.1016/j.cell.2017.11.048] [PMID: 29290465]
[113]
Kryukov, G.V.; Castellano, S.; Novoselov, S.V.; Lobanov, A.V.; Zehtab, O.; Guigó, R.; Gladyshev, V.N. Characterization of mammalian selenoproteomes. Science, 2003, 300(5624), 1439-1443.
[http://dx.doi.org/10.1126/science.1083516] [PMID: 12775843]
[114]
Warner, G.J.; Berry, M.J.; Moustafa, M.E.; Carlson, B.A.; Hatfield, D.L.; Faust, J.R. Inhibition of selenoprotein synthesis by selenocysteine tRNA[Ser]Sec lacking isopentenyladenosine. J. Biol. Chem., 2000, 275(36), 28110-28119.
[http://dx.doi.org/10.1074/jbc.M001280200] [PMID: 10821829]
[115]
Alim, I.; Caulfield, J.T.; Chen, Y.; Swarup, V.; Geschwind, D.H.; Ivanova, E.; Seravalli, J.; Ai, Y.; Sansing, L.H.; Ste Marie, E.J.; Hondal, R.J.; Mukherjee, S.; Cave, J.W.; Sagdullaev, B.T.; Karuppagounder, S.S.; Ratan, R.R. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell, 2019, 177(5), 1262-1279.e25.
[http://dx.doi.org/10.1016/j.cell.2019.03.032] [PMID: 31056284]
[116]
Shintoku, R.; Takigawa, Y.; Yamada, K.; Kubota, C.; Yoshimoto, Y.; Takeuchi, T.; Koshiishi, I.; Torii, S. Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3. Cancer Sci., 2017, 108(11), 2187-2194.
[http://dx.doi.org/10.1111/cas.13380] [PMID: 28837253]
[117]
Shimada, K.; Skouta, R.; Kaplan, A.; Yang, W.S.; Hayano, M.; Dixon, S.J.; Brown, L.M.; Valenzuela, C.A.; Wolpaw, A.J.; Stockwell, B.R. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat. Chem. Biol., 2016, 12(7), 497-503.
[http://dx.doi.org/10.1038/nchembio.2079] [PMID: 27159577]
[118]
Gaschler, M.M.; Andia, A.A.; Liu, H.; Csuka, J.M.; Hurlocker, B.; Vaiana, C.A.; Heindel, D.W.; Zuckerman, D.S.; Bos, P.H.; Reznik, E.; Ye, L.F.; Tyurina, Y.Y.; Lin, A.J.; Shchepinov, M.S.; Chan, A.Y.; Peguero-Pereira, E.; Fomich, M.A.; Daniels, J.D.; Bekish, A.V.; Shmanai, V.V.; Kagan, V.E.; Mahal, L.K.; Woerpel, K.A.; Stockwell, B.R. FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat. Chem. Biol., 2018, 14(5), 507-515.
[http://dx.doi.org/10.1038/s41589-018-0031-6] [PMID: 29610484]
[119]
Lee, J.; Zhou, H.J.; Wu, X.H. Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells. Cancer Chemother. Pharmacol., 2006, 57(2), 213-220.
[http://dx.doi.org/10.1007/s00280-005-0002-y] [PMID: 16075280]
[120]
Ba, Q.; Zhou, N.; Duan, J.; Chen, T.; Hao, M.; Yang, X.; Li, J.; Yin, J.; Chu, R.; Wang, H. Dihydroartemisinin exerts its anticancer activity through depleting cellular iron via transferrin receptor-1. PLoS One, 2012, 7(8)e42703
[http://dx.doi.org/10.1371/journal.pone.0042703] [PMID: 22900042]
[121]
Wang, Z.; Hu, W.; Zhang, J.L.; Wu, X.H.; Zhou, H.J. Dihydroartemisinin induces autophagy and inhibits the growth of iron-loaded human myeloid leukemia K562 cells via ROS toxicity. FEBS Open Bio, 2012, 2(1), 103-112.
[http://dx.doi.org/10.1016/j.fob.2012.05.002] [PMID: 23650588]
[122]
Zhou, H.J.; Wang, Z.; Li, A. Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression. Anticancer Drugs, 2008, 19(3), 247-255.
[http://dx.doi.org/10.1097/CAD.0b013e3282f3f152] [PMID: 18510170]
[123]
Kelter, G.; Steinbach, D.; Konkimalla, V.B.; Tahara, T.; Taketani, S.; Fiebig, H.H.; Efferth, T. Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. PLoS One, 2007, 2(8)e798
[http://dx.doi.org/10.1371/journal.pone.0000798] [PMID: 17726528]
[124]
Chen, G.Q.; Benthani, F.A.; Wu, J.; Liang, D.G.; Bian, Z.X.; Jiang, X.J. Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis. Cell Death Differ., 2020, 27(1), 242-254.
[http://dx.doi.org/10.1038/s41418-019-0352-3] [PMID: 31114026]
[125]
Kong, Z.; Liu, R.; Cheng, Y. Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed. Pharmacother., 2019, 109, 2043-2053.
[http://dx.doi.org/10.1016/j.biopha.2018.11.030] [PMID: 30551460]
[126]
Lin, R.; Zhang, Z.; Chen, L.; Zhou, Y.; Zou, P.; Feng, C.; Wang, L.; Liang, G. Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells. Cancer Lett., 2016, 381(1), 165-175.
[http://dx.doi.org/10.1016/j.canlet.2016.07.033] [PMID: 27477901]
[127]
Longxi, P.; Buwu, F.; Yuan, W.; Sinan, G. Expression of p53 in the effects of artesunate on induction of apoptosis and inhibition of proliferation in rat primary hepatic stellate cells. PLoS One, 2011, 6(10)e26500
[http://dx.doi.org/10.1371/journal.pone.0026500] [PMID: 22053192]
[128]
Wang, K.; Zhang, Z.; Wang, M.; Cao, X.; Qi, J.; Wang, D.; Gong, A.; Zhu, H. Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells. Drug Des. Devel. Ther., 2019, 13, 2135-2144.
[http://dx.doi.org/10.2147/DDDT.S199459] [PMID: 31456633]
[129]
Chen, Y.; Mi, Y.; Zhang, X.; Ma, Q.; Song, Y.; Zhang, L.; Wang, D.; Xing, J.; Hou, B.; Li, H.; Jin, H.; Du, W.; Zou, Z. Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells. J. Exp. Clin. Cancer Res., 2019, 38(1), 402.
[http://dx.doi.org/10.1186/s13046-019-1413-7] [PMID: 31519193]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy