Interaction studies of flavonoids with Bcl-2 protein to re-activate apoptosis in JurkatT-cells by induced TRAIL

Abstract

Immune cell malignancy such as Acute T- cell Lymphoblastic Leukaemia is generally associated with high rate of relapse and often does not respond to salvage therapy. Thus, identification of novel treatment regimens or cell apoptosis pathways and therapeutic agents without major side effects is necessary. TRAIL-induced apoptotic pathway is one such pathway that is usually blocked by anti-apoptotic proteins like Bcl-2. This research estimated and compared the ability of few common flavonoids to re-activate TRAIL-induced apoptosis by blocking Bcl-2 protein. Studies were carried out to understand the interaction between binding energy of the Flavonoids with Bcl-2 protein in cancer cells. The pharmacokinetic and toxicity profiling was performed to study the potency of the flavonoids as a lead candidate. Baicalein was selected as lead molecule because of its lower binding energy and its ability to increase Mitochondrial Membrane Potential as studied from its ADME properties. For validation of apoptosis of Baicalein by TRAIL-induced owing to Bcl-2 analysis of cell cycle and Gene expression studies were carried out on Jurkat T cells.