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Issue 1, 2017
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Withaferin A induces cell death and differentiation in multiple myeloma cancer stem cells

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Abstract

Multiple myeloma (MM) remains an incurable malignancy despite the development of novel therapeutics. This is believed to be due to a subset of rare chemotherapy-resistant cancer stem cells (CSCs). Differentiation therapy represents one strategy aimed at reducing the stemness of CSCs. The anticancer effect of withaferin A (WFA) was studied in MM-CSCs and RPMI 8226 MM tumoral plasma cells (RPMIs). WFA exhibited growth inhibitory effects in both MM-CSCs and RPMIs, with IC50 values of 649 and 224 nM, respectively. WFA also induced a G2 cell cycle arrest, as well as cell death and apoptosis. Although, WFA did not exhibit a direct anti-migratory effect, a remarkable morphological change was observed in MM-CSCs in response to WFA treatment. Using qPCR gene expression analyses, WFA caused a reduction in stemness markers, and a promotion of differentiation markers in MM-CSCs. These results warrant further investigation of WFA in relevant MM animal models.

Graphical abstract: Withaferin A induces cell death and differentiation in multiple myeloma cancer stem cells

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Supplementary files

Article information


Submitted
19 Jul 2016
Accepted
17 Nov 2016
First published
17 Nov 2016

, 2017,8, 112-121
Article type
Research Article

Withaferin A induces cell death and differentiation in multiple myeloma cancer stem cells

M. E. Issa and M. Cuendet, , 2017, 8, 112
DOI: 10.1039/C6MD00410E

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