Research Progress on Anti-tumor Mechanism of Artesunate Combined Drugs

Mengting Shi; Xiulan Yang

doi:10.54097/jhbxr864

Authors

Mengting Shi
Xiulan Yang

DOI:

https://doi.org/10.54097/jhbxr864

Keywords:

Artesunate; Anti-tumor; Drug combination; Action mechanism.

Abstract

Artesunate (ART) is a semi-synthetic artemisinin derivative of hemiterpene lactones, which is widely used in clinical antimalarial therapy. In recent years, studies have shown that artesunate also has anti-inflammatory, anti-tumor, anti-fibrosis, antiviral, antibacterial, immunomodulatory and other pharmacological activities. Artesunate can play an anti-tumor role by inhibiting tumor cell proliferation, invasion and migration, promoting tumor cell apoptosis and blocking cell cycle. At the same time, when combined with other anti-tumor drugs, it can enhance the anti-tumor efficacy, shorten the duration of administration, reduce the dose and adverse reactions. In this paper, the main keywords of "artesunate", "pharmacology", "anti-tumor" and "combined drug" were searched and integrated in Pubmed, Web of Science and CNKI electronic databases to review the anti-tumor mechanism of artesunate combined with other drugs in recent 5 years. The prospect of clinical application of artesunate as an antitumor drug was prospected to provide some theoretical basis for further rational development and utilization of artesunate and new drug research and development.

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References

Qi J, Li M, Wang L, Hu Y, Liu W, Long Z, Zhou Z, Yin P, Zhou M. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data. Lancet Public Health. 2023 Dec;8(12):e943-e955. doi: 10.1016/S2468-2667(23)00211-6. PMID: 38000889.

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. PMID: 36633525.

Maomao C, He L, Dianqin S, Siyi H, Xinxin Y, Fan Y, Shaoli Z, Changfa X, Lin L, Ji P, Wanqing C. Current cancer burden in China: epidemiology, etiology, and prevention. Cancer Biol Med. 2022 Aug 30;19(8):1121–38. doi: 10.20892/j.issn.2095-3941.2022.0231. PMID: 36069534; PMCID: PMC9425189.

Papież MA, Krzyściak W. Biological Therapies in the Treatment of Cancer-Update and New Directions. Int J Mol Sci. 2021 Oct 28;22(21):11694. doi: 10.3390/ijms222111694. PMID: 34769123; PMCID: PMC8583892.

Nasir A, Khan A, Li J, Naeem M, Khalil AAK, Khan K, Qasim M. Nanotechnology, A Tool for Diagnostics and Treatment of Cancer. Curr Top Med Chem. 2021;21(15):1360-1376. doi: 10.2174/1568026621666210701144124. PMID: 34218784.

Sivadasan D, Ramakrishnan K, Mahendran J, Ranganathan H, Karuppaiah A, Rahman H. Solid Lipid Nanoparticles: Applications and Prospects in Cancer Treatment. Int J Mol Sci. 2023 Mar 24;24(7):6199. doi: 10.3390/ijms24076199. PMID: 37047172; PMCID: PMC10094605.

Ruwizhi N, Maseko RB, Aderibigbe BA. Recent Advances in the Therapeutic Efficacy of Artesunate. Pharmaceutics. 2022 Feb 25;14(3):504. doi: 10.3390/pharmaceutics14030504. PMID: 35335880; PMCID: PMC8951414.

Huang Z, Gan S, Zhuang X, Chen Y, Lu L, Wang Y, Qi X, Feng Q, Huang Q, Du B, Zhang R, Liu Z. Artesunate Inhibits the Cell Growth in Colorectal Cancer by Promoting ROS-Dependent Cell Senescence and Autophagy. Cells. 2022 Aug 9;11(16):2472. doi: 10.3390/cells11162472. PMID: 36010550; PMCID: PMC9406496.

Xu Z, Liu X, Zhuang D. Artesunate inhibits proliferation, migration, and invasion of thyroid cancer cells by regulating the PI3K/AKT/FKHR pathway. Biochem Cell Biol. 2022 Feb;100(1):85-92. doi: 10.1139/bcb-2021-0275. Epub 2021 Nov 19. PMID: 34797728.

Wang L, Liu L, Wang J, Chen Y. Inhibitory Effect of Artesunate on Growth and Apoptosis of Gastric Cancer Cells. Arch Med Res. 2017 Oct;48(7):623-630. doi: 10.1016/j.arcmed.2018.03.004. Epub 2018 Mar 12. PMID: 29544887.

Zhou X, Chen Y, Wang F, Wu H, Zhang Y, Liu J, Cai Y, Huang S, He N, Hu Z, Jin X. Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. Chem Biol Interact. 2020 Nov 1;331:109273. doi: 10.1016/j.cbi.2020.109273. Epub 2020 Sep 28. PMID: 33002460.

Karati D, Mahadik KR, Trivedi P, Kumar D. Alkylating Agents, the Road Less Traversed, Changing Anticancer Therapy. Anticancer Agents Med Chem. 2022;22(8):1478-1495. doi: 10.2174/1871520621666210811105344. PMID: 34382529.

Costa BA, Mouhieddine TH, Ortiz RJ, Richter J. Revisiting the role of alkylating agents in multiple myeloma: Up-to-date evidence and future perspectives. Crit Rev Oncol Hematol. 2023 Jul;187:104040. doi: 10.1016/j.critrevonc.2023.104040. Epub 2023 May 25. PMID: 37244325.

Ismail M, Yang W, Li Y, Chai T, Zhang D, Du Q, Muhammad P, Hanif S, Zheng M, Shi B. Targeted liposomes for combined delivery of artesunate and temozolomide to resistant glioblastoma. Biomaterials. 2022 Aug;287:121608. doi: 10.1016/j.biomaterials.2022.121608. Epub 2022 Jun 1. PMID: 35690021.

Takeuchi T. Antitumor antibiotics discovered and studied at the Institute of Microbial Chemistry. J Cancer Res Clin Oncol. 1995;121(9-10):505-10. doi: 10.1007/BF01197761. PMID: 7559728.

Chandy M, Conklin DJ. Recent advances in the cardiotoxicity of anti-cancer drugs: Navigating the landscape of anthracycline-induced cardiotoxicity. Toxicol Appl Pharmacol. 2024 Jan;482:116791. doi: 10.1016/j.taap.2023.116791. Epub 2023 Dec 14. PMID: 38103743.

Efferth T, Giaisi M, Merling A, Krammer PH, Li-Weber M. Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One. 2007 Aug 1;2(8):e693. doi: 10.1371/journal.pone.0000693. PMID: 17668070; PMCID: PMC1933253.

Duarte D, Nunes M, Ricardo S, Vale N. Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action. Biomolecules. 2022 Oct 16;12(10):1490. doi: 10.3390/biom12101490. PMID: 36291699; PMCID: PMC9599492.

Oun R , Moussa YE , Wheate NJ . The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018 May 15;47(19):6645-6653. doi: 10.1039/c8dt00838h. Erratum in: Dalton Trans. 2018 Jun 12;47(23):7848. PMID: 29632935.

Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. 2022 Feb 7;12(5):2115-2132. doi: 10.7150/thno.69424. PMID: 35265202; PMCID: PMC8899578.

Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019 Nov;575(7782):299-309. doi: 10.1038/s41586-019-1730-1. Epub 2019 Nov 13. PMID: 31723286; PMCID: PMC8008476.

Qi L, Luo Q, Zhang Y, Jia F, Zhao Y, Wang F. Advances in Toxicological Research of the Anticancer Drug Cisplatin. Chem Res Toxicol. 2019 Aug 19;32(8):1469-1486. doi: 10.1021/acs.chemrestox.9b00204. Epub 2019 Aug 5. PMID: 31353895.

Liu W, Yu C, Wang M, He Y, Guo Z, He J, Jiang R, Xu Q, Liang J, Wang S. Discovery of PlatinumIV-Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents. J Med Chem. 2023 Jun 22;66(12):8066-8085. doi: 10.1021/acs.jmedchem.3c00396. Epub 2023 Jun 12. PMID: 37306362.

Li W, Ma G, Deng Y, Wu Q, Wang Z, Zhou Q. Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway. Gene. 2021 Jan 15;766:145134. doi: 10.1016/j.gene.2020.145134. Epub 2020 Sep 6. PMID: 32898605.

Wang Z, Wang Q, He T, Li W, Liu Y, Fan Y, Wang Y, Wang Q, Chen J. The combination of artesunate and carboplatin exerts a synergistic anti-tumour effect on non-small cell lung cancer. Clin Exp Pharmacol Physiol. 2020 Jun;47(6):1083-1091. doi: 10.1111/1440-1681.13287. Epub 2020 Mar 20. PMID: 32072678.

Ciaffaglione V, Modica MN, Pittalà V, Romeo G, Salerno L, Intagliata S. Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs. ChemMedChem. 2021 Dec 6;16(23):3496-3512. doi: 10.1002/cmdc.202100473. Epub 2021 Sep 7. PMID: 34415107; PMCID: PMC9290623.

Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, Herrmann J, Lerman A, Grothey A. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018 Jun 18;10:1758835918780140. doi: 10.1177/1758835918780140. PMID: 29977352; PMCID: PMC6024329.

Xia J, Dai QL, He S, Jia HJ, Liu XG, Hua H, Zhou M, Wang X. Artesunate alleviates 5-fluorouracil-induced intestinal damage by suppressing cellular senescence and enhances its antitumor activity. Discov Oncol. 2023 Jul 27;14(1):139. doi: 10.1007/s12672-023-00747-7. PMID: 37498338; PMCID: PMC10374509.

Li JY, Xiong X, Wang DW, Zhang XY, Huang C, Zou LL, Zheng CF, Chen X, Tu CQ. [The Mechanism of Artesunate Combined with Cytarabine and/or Daunorubicin on the Apoptosis of MV4-11 MLL-rearranged Acute Myeloid Leukemia Cell Line]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Dec;30(6):1724-1729. Chinese. doi: 10.19746/j.cnki.issn.1009-2137.2022.06.015. PMID: 36476895.

Zhang J, Wang Y, Yin C, Gong P, Zhang Z, Zhao L, Waxman S, Jing Y. Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis. Cell Death Dis. 2022 Apr 20;13(4):379. doi: 10.1038/s41419-022-04810-z. PMID: 35443722; PMCID: PMC9021233.

Su Q, Huang P, Luo X, Zhang P, Li H, Chen Y. Artesunate reverses cytarabine resistance in acute myeloid leukemia by blocking the JAK/STAT3 signaling. Hematology. 2023 Dec;28(1):2255802. doi: 10.1080/16078454.2023.2255802. Epub 2023 Oct 10. PMID: 37815490.

Efferth T. Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib. Phytomedicine. 2017 Dec 15;37:58-61. doi: 10.1016/j.phymed.2017.11.003. Epub 2017 Nov 10. PMID: 29174651.

Yao X, Zhao CR, Yin H, Wang K, Gao JJ. Synergistic antitumor activity of sorafenib and artesunate in hepatocellular carcinoma cells. Acta Pharmacol Sin. 2020 Dec;41(12):1609-1620. doi: 10.1038/s41401-020-0395-5. Epub 2020 Apr 16. PMID: 32300243; PMCID: PMC7921114.

Li ZJ, Dai HQ, Huang XW, Feng J, Deng JH, Wang ZX, Yang XM, Liu YJ, Wu Y, Chen PH, Shi H, Wang JG, Zhou J, Lu GD. Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma. Acta Pharmacol Sin. 2021 Feb;42(2):301-310. doi: 10.1038/s41401-020-0478-3. Epub 2020 Jul 22. PMID: 32699265; PMCID: PMC8026986.

Chen M, Wu HL, Wong TS, Chen B, Gong RH, Wong HLX, Xiao H, Bian Z, Kwan HY. Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis. Front Pharmacol. 2021 May 5;12:657080. doi: 10.3389/fphar.2021.657080. PMID: 34025421; PMCID: PMC8131852.

Chen YJ, Wu JY, Deng YY, Wu Y, Wang XQ, Li AS, Wong LY, Fu XQ, Yu ZL, Liang C. Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models. J Ginseng Res. 2022 May;46(3):418-425. doi: 10.1016/j.jgr.2021.07.002. Epub 2021 Jul 14. PMID: 35600776; PMCID: PMC9120623.

Jiu X, Liu Y, Wen J. Artesunate combined with verteporfin inhibits uveal melanoma by regulation of the MALAT1/yes-associated protein signaling pathway. Oncol Lett. 2021 Aug;22(2):597. doi: 10.3892/ol.2021.12858. Epub 2021 Jun 9. PMID: 34188699; PMCID: PMC8228376.

Hu LJ, Jiang T, Wang FJ, Huang SH, Cheng XM, Jia YQ. [Effects of artesunate combined with bortezomib on apoptosis and autophagy of acute myeloid leukemia cells in vitro and its mechanism]. Zhonghua Xue Ye Xue Za Zhi. 2019 Mar 14;40(3):204-208. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2019.03.008. PMID: 30929387; PMCID: PMC7342538.

Li H, Xu K, Pian G, Sun S. Artesunate and sorafenib: Combinatorial inhibition of liver cancer cell growth. Oncol Lett. 2019 Nov;18(5):4735-4743. doi: 10.3892/ol.2019.10810. Epub 2019 Sep 5. PMID: 31611983; PMCID: PMC6781774.

Chen CP, Chen K, Feng Z, Wen X, Sun H. Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis via synergistic upregulation of ALAS1 expression. Acta Pharm Sin B. 2019 Sep;9(5):937-951. doi: 10.1016/j.apsb.2019.05.001. Epub 2019 May 23. PMID: 31649844; PMCID: PMC6804493.

Jing W, Shuo L, Yingru X, Min M, Runpeng Z, Jun X, Dong H. Artesunate promotes sensitivity to sorafenib in hepatocellular carcinoma. Biochem Biophys Res Commun. 2019 Oct 29;519(1):41-45. doi: 10.1016/j.bbrc.2019.08.115. Epub 2019 Aug 31. PMID: 31481232.

Yang T, Zhang S, Yuan H, Wang Y, Cai L, Chen H, Wang X, Song D, Wang X, Guo Z, Wang X. Platinum-Based TREM2 Inhibitor Suppresses Tumors by Remodeling the Immunosuppressive Microenvironment. Angew Chem Int Ed Engl. 2023 Jan 9;62(2):e202213337. doi: 10.1002/anie.202213337. Epub 2022 Dec 7. PMID: 36259513.