Tanya Das
Bose Institute, India
Scientific Tracks Abstracts: Nat Prod Chem Res
The adverse side-effects associated with chemotherapy during cancer treatment have shifted considerable focus towards therapies that are targeted but devoid of toxic side-effects. In the present study, the anti-tumorigenic activity of Thuja, the bioactive derivative of the medicinal plant Thuja occidentalis, was evaluated, and the molecular mechanisms underlying Thujainduced apoptosis of functional p53-expressing mammary epithelial carcinoma cells were elucidated. Our results showed that Thuja successfully induced apoptosis in functional p53-expressing mammary epithelial carcinoma cells. Abrogation of intracellular Reactive Oxygen Species (ROS), prevention of p53-activation, knockdown of p53 or inhibition of its functional activity significantly abridged ROS generation. Notably, under these conditions, Thuja-induced breast cancer cell apoptosis was reduced, thereby validating the existence of an ROS-p53 feedback loop. Elucidating this feedback loop revealed bi-phasic ROS generation as a key mediator of Thuja-induced apoptosis. Thuja-induced generation of ROS at the first phase was instrumental in ensuring activation of p53 via p38MAPK and its nuclear translocation for transactivation of Bax, which induced a second phase of mitochondrial ROS to construct the ROS-p53 feedback loop. Such molecular crosstalk induced mitochondrial changes 1) to maintain and amplify the Thuja signal in a positive self-regulatory feedback manner; and 2) to promote the mitochondrial death cascade through cytochrome c release and caspase-driven apoptosis. These results open the horizon for developing a targeted therapy by modulating the redox status of functional p53-expressing mammary epithelial carcinoma cells by Thuja.
Tanya Das completed her PhD at University of Calcutta, India, Currently she is working at the Division of Molecular Medicine as a Senior Professor, She has been a Post-doctoral Fellow and Research Associate, at Calcutta University, Kolkata from 1990-1996, and Research Scientist at Bose Institute, Kolkata, She has published more than 50 papers in reputed journals.
Email: tanya@jcbose.ac.in
