Ashwagandha is an exotic Indian herb which has remarkable stress-relieving properties. In addition to its excellent protective effects on the nervous system
may be a promising alternative treatment for a variety of degenerative diseases such as Alzheimer's
and Parkinson's. AshwaganDHA
has powerful antioxidant
properties that seek and destroy the free radicals
that have been implicated in aging
and numerous disease
states. Even more remarkable, emerging evidence suggests that ashwaganDHA
has anti-cancer benefits as well.
Lee J, Hahm ER, Singh SV. Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human Breast cancer cells. 1. Carcinogenesis. 2010 Nov;31(11):1991-8. Epub 2010 Aug 19.
We have shown previously that withaferin A (WA), a promising anticancer constituent of Ayurvedic medicine plant Withania somnifera, inhibits growth of human Breast cancer cells in culture and in vivo in association with apoptosis induction. The present study builds on these observations and demonstrates that WA inhibits constitutive as well as interleukin-6 (IL-6)-inducible activation of signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor activated in many human malignancies including Breast cancer. The WA treatment (2 and 4 ?M) decreased constitutive (MDA-MB-231) and/or IL-6-inducible (MDA-MB-231 and MCF-7) phosphorylation of STAT3 (Tyr(705 border=0> and its upstream regulator Janus-activated kinase 2 (JAK2; Tyr(1007/1008 border=0> in MDA-MB-231, which was accompanied by suppression of their protein levels especially at the higher concentration. Exposure of MDA-MB-231 or MCF-7 cells to WA also resulted in suppression of (i) transcriptional activity of STAT3 with or without IL-6 stimulation in both cells; (ii) dimerization of STAT3 (MDA-MB-231) and (iii) nuclear translocation of Tyr(705)-phosphorylated STAT3 in both cells. To our surprise, the IL-6-stimulation, either before or after WA treatment, did not have an appreciable effect on WA-mediated apoptosis in MDA-MB-231 or MCF-7 cell line. The IL-6-stimulated activation of STAT3 conferred a modest protection against WA-mediated suppression of MDA-MB-231 cell invasion. General implication of these findings is that WA can trigger apoptosis and largely inhibit cell migration/invasion of Breast cancer cells even after IL-6-induced activation of STAT3, which should be viewed as a therapeutic advantage for this agent.