NDLI: Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2

Content Provider	Springer Nature Link
Author	Mayola, Eleore Gallerne, Cindy Esposti, Davide Degli Martel, Cecile Pervaiz, Shazib Larue, Lionel Debuire, Brigitte Lemoine, Antoinette Brenner, Catherine Lemaire, Christophe
Copyright Year	2011
Abstract	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 μM. 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 (ΔΨm) 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.
Starting Page	1014
Ending Page	1027
Page Count	14
File Format	PDF
ISSN	13608185
Journal	Apoptosis
Volume Number	16
Issue Number	10
e-ISSN	1573675X
Language	English
Publisher	Springer US
Publisher Date	2011-06-28
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Melanoma resistance Cell death Oncogene Chemotherapy Oncology Cell Biology Cancer Research Virology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology

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