You are here: Home Research Ashwagandha

Withaferin a Induces P53-Dependent Apoptosis by Repression of HPV Oncogenes and Upregulation of Tumor Suppressor Proteins in Human Cervical Cancer Cells

Posted by Admin on Wednesday, August 15, 2012
© Authored by PubMed
© HealthyMuslim. See Terms and Conditions

 Copy Link
   Email    Print 
Ashwagandha is an exotic Indian herb which has remarkable stress-relieving properties. In addition to its excellent protective effects on the nervous system, ashwaganDHA 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.

Munagala R, Kausar H, Munjal C, Gupta RC. Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. 1. Carcinogenesis. 2011 Nov;32(11):1697-705. Epub 2011 Aug 22.

Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ? 0.05 ?M). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects.


Link to this article:   Show: HTML LinkFull LinkShort Link
Share or Bookmark this page: You will need to have an account with the selected service in order to post links or bookmark this page.

                 
  
Subscribe via RSS or email:
Follow us through RSS or email. Click the RSS icon to subscribe to our feed.

     
  

Related Articles:
Add a Comment
You must be registered and logged in to comment.
Most Popular

Latest Articles

Popular Subjects
fluoridewater fluoridationcolicfruitexercisetoothpastealmondsmilkpHalkalineacidVitamin Ccancerlinus paulingwatercell phonemobile phoneraw milkaspartamesweetenersuperfoodsbrainlong lifelive longlongevityresveratrolblueberriesraspberriesgreen teaavocadosfatsnutritiondigestion research

Health, fitness and longevity
 Based upon the principles of health
 in the Qur'an and Prophetic Traditions.
HealthyMuslim.Com

There are two bounties in which
most people lose out: good health
and free time. Al-Bukhari.
The information on this site is provided for educational purposes only. It is not intended as a substitute for professional advice of any kind.