Withaferin A is effective in inhibiting the survival of B cell lymphomas and chronic lymphocytic leukemias (P2052)

Abstract Withaferin A is a withanolide from the ayurvedic medicinal plant, Withania Somnifera that has been shown to be a major contributor to the medicinal value of extracts from this plant. Withanolides, oxidation products of steroids, are known to have growth inhibitory effects on certain insect larvae. Withaferin A is the first withanolide to be isolated from the Aswagandha plant. It has been shown to have anticancer activity in breast and lung cancer models but its effects on hematological malignancies have not been studied in detail. Here we examined the effect of highly purified Withaferin A on the survival of diffuse large B cell lymphoma cell lines. Withaferin A strongly inhibited the survival of Ramos, Sudhl6, LY10 and murine A20luc and BKS2 B cell lymphoma cell lines, mainly by affecting cell cycle progression. It also reduced the survival of chronic lymphocytic leukemia cells (CLL) from the Emu-Tcl1 transgenic mice. We found that Withaferin A inhibited activation of Akt rapidly but of Src family kinase after 24 hours of incubation and also reduced the levels of pro-survival protein Bcl-x, in the murine CLL cells Withaferin A also reduced the levels of the pro-survival oncogene Tcl1 as well as the pro-apoptotic protein Par-4. We are currently investigating the mechanisms that underlie the opposite effects (reduction of both pro-survival and anti-survival proteins) and their relation to the anti-lymphoma/leukemia effects of Withaferin A.