Issue 1, 2017

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

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

Supplementary files

Article information

Article type
Research Article
Submitted
19 Jul 2016
Accepted
17 Nov 2016
First published
17 Nov 2016

Med. Chem. Commun., 2017,8, 112-121

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

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

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