title: Anti-cancer activity of withaferin A in B-cell lymphoma.
abstract: 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.
authors.affiliation: a Department of Microbiology, Immunology and Molecular Genetics; Markey Cancer Center; University of Kentucky ; Lexington , KY , USA.
authors.forename: M K
authors.initials: MK
authors.lastname: McKenna
authors.forename: B W
authors.initials: BW
authors.lastname: Gachuki
authors.forename: S S
authors.initials: SS
authors.lastname: Alhakeem
authors.forename: K N
authors.initials: KN
authors.lastname: Oben
authors.forename: V M
authors.initials: VM
authors.lastname: Rangnekar
authors.forename: R C
authors.initials: RC
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Bondada
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D047368:Tumor Burden / Q000187:drug effects; D032341:Withania / Q000737:chemistry; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018841:HSP90 Heat-Shock Proteins; D016328:NF-kappa B; D054358:Withanolides; C009684:withaferin A
keywords: B-cell lymphoma; B-cell receptor signaling; DLBCL, Diffuse large B cell lymphoma; WA, Withaferin A; apoptosis; withaferin A