Withaferin A inhibits cell proliferation of U266B1 and IM-9 human myeloma cells by inducing intrinsic apoptosis

Lan Li; Ben Niu; Weihua Zhang; Limin Hou; Yan Zheng

doi:10.18388/abp.2020_5938

Withaferin A inhibits cell proliferation of U266B1 and IM-9 human myeloma cells by inducing intrinsic apoptosis

Lan Li Department of hematopathology, Shaanxi Provincial People’s Hospital, Xi ‘an, Shaanxi, China
Ben Niu Department of hematopathology, Shaanxi Provincial People’s Hospital, Xi ‘an, Shaanxi, China
Weihua Zhang Department of hematopathology, Shaanxi Provincial People’s Hospital, Xi ‘an, Shaanxi, China
Limin Hou Department of hematopathology, Shaanxi Provincial People’s Hospital, Xi ‘an, Shaanxi, China
Yan Zheng Department of hematopathology, Shaanxi Provincial People’s Hospital, Xi ‘an, Shaanxi, China

DOI: https://doi.org/10.18388/abp.2020_5938

Abstract

Withaferin A, a withanolide obtained from Withania somnifera exhibits remarkable pharmacological properties. Withaferin A has been reported to exert cytotoxic effects against human multiple myeloma cells. Nevertheless, the in-depth understanding of the withaferin A induced antiproliferative effects against human myeloma cells is still unclear. The results showed that withaferin A inhibited the viability of six different myeloma cells with a lowest IC50 of 9 μM against the U266B1 and IM-9 cell lines. Withaferin A inhibited the viability and colony formation of the U266B1 and IM-9 cells in a dose and time-dependent manner. The DAPI and annexin V/PI staining assays revealed that withaferin A exerts anticancer effects against the human myeloma cells via induction of apoptosis. The induction of apoptosis in U266B1 and IM-9 cells was associated with upregulation of Bax and cytochrome c, downregulation of Bcl-2 and activation of PARP, caspase-3 and capase-9 cleavage. Additionally, withaferin A triggered the production of ROS in human myeloma cells indicative of ROS mediated apoptosis in human myeloma cells. The treatment of the U266B1 and IM-9 with ascorbic acid (antioxidant) could prevent the withaferin A mediated ROS production and the withaferin A induced antiproliferative effects. Collectively, the results show that withaferin A inhibits human myeloma cell proliferation via ROS mediated intrinsic apoptosis.

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Published

2022-03-02

Issue

Vol. 69 No. 1 (2022)

Section

Articles

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