Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells
Language: 
English
Abstract: 

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 μM) decreased constitutive (MDA-MB-231) and/or IL-6-inducible (MDA-MB-231 and MCF-7) phosphorylation of STAT3 (Tyr(705)) and its upstream regulator Janus-activated kinase 2 (JAK2; Tyr(1007/1008)) 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.

Author(s): 
Lee, Joomin
Hahm, Eun-Ryeong
Singh, Shivendra V.
Item Type: 
Journal Article
Publication Title: 
Carcinogenesis
Journal Abbreviation: 
Carcinogenesis
Publication Date: 
Nov 2010
Publication Year: 
2010
Pages: 
1991-1998
Volume: 
31
Issue: 
11
ISSN: 
1460-2180
DOI: 
10.1093/carcin/bgq175
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 20724373 PMCID: PMC2966554

Turabian/Chicago Citation

Joomin Lee, Eun-Ryeong Hahm and Shivendra V. Singh. Nov 2010. "Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells." Carcinogenesis 31: 11: 1991-1998. 10.1093/carcin/bgq175.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/carcin/bgq175 | issn = 1460-2180 | volume = 31 | pages = 1991-1998 | last = Lee | first = Joomin | coauthors = Hahm, Eun-Ryeong, Singh, Shivendra V. | title = Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells | journal = Carcinogenesis | date = Nov 2010 | pmid = | pmc = }} </ref>