Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90.
|Number of pages||11|
|Journal||Cancer Biology and Therapy|
|State||Published - Jan 1 2015|
Bibliographical noteFunding Information:
We thank UK Flow Cytometry and Cell Sorting Core Facility, and the small animal imaging facility which is supported in part by the Office of the Vice President for Research, the Markey Cancer Center and an NCI Center Core Support Grant (P30 CA177558) to the University of Kentucky Markey Cancer Center. This research was funded by NIH Grants R01 CA165469, T32 CA165990, Agnes Brown Duggan Endowment (RG), and the Edwards P Evans Foundation.
© 2015 Taylor and Francis Group, LLC.
- B-cell lymphoma
- B-cell receptor signaling
- Withaferin A
ASJC Scopus subject areas
- Molecular Medicine
- Cancer Research