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Korean Journal of Clinical Oncology > Volume 16(2); 2020 > Article
ORIGINAL ARTICLE
Korean J Clin Oncol. 2020;16(2): 131-137.         doi: https://doi.org/10.14216/kjco.20020
YM155, specific survivin inhibitor, can enhance artesunate-induced cytotoxicity in HCT116 colon cancer cells
Eui Tae Kim , Dong-Guk Park
Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
Corresponding Author: Dong-Guk Park ,Tel: +82-41-550-3931, Fax: +82-41-565-6167, Email: dkpark@dankook.ac.kr
Received: September 26, 2020;  Accepted: November 18, 2020.
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ABSTRACT
Purpose: A water-soluble variant of the artemisinin called artesunate, approved as an antimalarial agent, can induce cell death on various cancer cell types. We studied the mechanism of cell death of artesunate on HCT116 colorectal cancer cells.
Methods: We treated HCT116 colon cancer cells with artesunate, holo-transferrin, deferoxamine mesylate, ferrostatin, necrostatin-1, and YM155. We observed the growth inhibition of artesunate on HCT116 colon cancer cells by morphologic findings. Inhibition of cell growth was assessed by MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay and long-term growth inhibition by colony-forming assay. Apoptosis was investigated by flow cytometry and Western blot analysis.
Results: Artesunate inhibited the proliferation of HCT116 colon cancer cells effectively. Co-treatment with YM155, a specific survivin inhibitor, enhanced the artesunate-induced cell death. Co-treatment with the iron-chelating agent deferoxamine rescued artesunate induced cell death and increased long-term cell survival and proliferation.
Conclusion: In this study, we demonstrated that artesunate-induced cytotoxicity in HCT116 colon cancer cells by suppressing the expression of survivin and partially by ferroptosis. Our findings suggest that the co-treatment artesunate with YM155 can induce more potent cell death on HCT116 colon cancer cells and shows new insight for the treatment of colorectal cancer patients.
Keywords: YM155 | Artesunate | Survivin | Necroptosis | Ferroptosis
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