Description
Withaferin A is a steroid lactone initially produced by Withania somnifera that exhibits anticancer chemotherapeutic, chemopreventive, and anti-inflammatory activities. Withaferin A inhibits vimentin, an intermediate filament, preventing breast cancer cell growth in vitro and in vivo. Withaferin A also increases phosphorylation of JNK, ERK, and p38 MAPK and increases levels of Mcl-1, inducing apoptosis in other in vitro models of breast cancer. Across other breast cancer cell lines, withaferin A increases activation of p53, downregulates expression of ERα, and activates Notch4 and Notch4, inhibiting cellular migration and growth. In ovarian cancer cells, withaferin A downregulates expression of Notch1, Notch3, chc25C, Akt, and Bcl-2, inhibiting growth and colony formation. Withaferin A also inhibits tumor growth of pancreatic xenografts in vivo through ATP-independent inhibition of heat shock protein 90 (HSP90). Additionally, this compound inhibits phosphorylation of IκB kinase, activation of NF-κB, and decreases levels of NO and iNOS in vitro.
References
Antony ML, Lee J, Hahm ER, et al. Growth Arrest by the Antitumor Steroidal Lactone Withaferin A in Human Breast Cancer Cells Is Associated with Downregulation and Covalent Binding at Cysteine-303 of β-Tubulin. J Biol Chem. 2013 Dec 2. [Epub ahead of print]. PMID: 24297176.
Hahm ER, Lee J, Singh SV. Role of mitogen-activated protein kinases and Mcl-1 in apoptosis induction by withaferin A in human breast cancer cells. Mol Carcinog. 2013 Sep 9. [Epub ahead of print]. PMID: 24019090.
Lee J, Sehrawat A, Singh SV. Withaferin A causes activation of Notch4 and Notch4 in human breast cancer cells. Breast Cancer Res Treat. 2012 Nov;136(1):45-56. PMID: 22965833.
Zhang X, Samadi AK, Roby KF, et al. Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A. Gynecol Oncol. 2012 Mar;124(3):606-12. PMID: 22188785.
Hahm ER, Lee J, Huang Y, et al. Withaferin a suppresses estrogen receptor-α expression in human breast cancer cells. Mol Carcinog. 2011 Aug;50(8):614-24. PMID: 21432907.
Yu Y, Hamza A, Zhang T, et al. Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem Pharmacol. 2010 Feb 15;79(4):542-51. PMID: 19769945.
Oh JH, Lee TJ, Park JW, et al. Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation and down-regulating LPS-induced activity of NF-kappaB in RAW 264.7 cells. Eur J Pharmacol. 2008 Dec 3;599(1-3):11-7. PMID: 18838070.
