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Withaferin a Induces Apoptosis in Human Melanoma Cells Through Generation of Reactive Oxygen Species and Down-Regulation of Bcl-2

Posted by Admin on Wednesday, August 15, 2012
Authored by PubMed

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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.

Mayola E, Gallerne C, Esposti DD, Martel C, Pervaiz S, Larue L, Debuire B, Lemoine A, Brenner C, Lemaire C. Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2. 1. Apoptosis. 2011 Oct;16(10):1014-27.
A high resistance and heterogeneous response to conventional anti-cancer chemotherapies characterize malignant cutaneous melanoma, the most aggressive and deadly form of skin cancer. Withaferin A (WFA), a withanolide derived from the medicinal plant Withania somnifera, has been reported for its anti-tumorigenic activity against various cancer cells. For the first time, we examined the death-inducing potential of WFA against a panel of four different human melanoma cells and investigated the cellular mechanisms involved. WFA induces apoptotic cell death with various IC50 ranging from 1.8 to 6.1 ?M. The susceptibility of cells toward WFA-induced apoptosis correlated with low Bcl-2/Bax and Bcl-2/Bim ratios. In all cell lines, the apoptotic process triggered by WFA involves the mitochondrial pathway and was associated with Bcl-2 down regulation, Bax mitochondrial translocation, cytochrome c release into the cytosol, transmembrane potential (??m) dissipation, caspase 9 and caspase 3 activation and DNA fragmentation. WFA cytotoxicity requires early reactive oxygen species (ROS) production and glutathione depletion, the inhibition of ROS increase by the antioxidant N-acetylcysteine resulting in complete suppression of mitochondrial and nuclear events. Altogether, these results support the therapeutic potential of WFA against human melanoma.


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