Fisetin induces G0/G1 arrest and apoptosis via mTOR signalling in HSC-3 cells
Selvaraj Jayaraman, Ramya Murali, Vishnu Priya VeeraraghavanAbstract
Background:
Oral carcinoma poses a significant health challenge, necessitating the exploration of novel therapeutic agents. Fisetin, a natural flavonoid, has demonstrated anti-cancer properties, yet its precise molecular mechanisms in oral carcinoma remain unclear. This study evaluates the cytotoxic and anti-proliferative effects of fisetin on the HSC-3 cell line, focusing on its impact on mTOR-mediated signalling pathways.
Aim:
To investigate the cytotoxic potential of fisetin in HSC-3 cells by assessing its effects on cell viability, gene expression, and protein interactions, highlighting its role in proliferation inhibition and apoptosis induction.
Materials and Methods:
HSC-3 cells were treated with varying fisetin concentrations. Cytotoxicity was assessed using an MTT assay to determine the IC 50 value. q-RT-PCR analysed the expression of mTOR pathway-related genes (4EBP1, Glut1, PKM2, RAPTOR, S6K1, and SGK1). Molecular docking simulations evaluated fisetin’s binding interactions with target proteins.
Results:
MTT assays revealed a dose-dependent cytotoxic effect of fisetin, with a significant IC 50 value. q-RT-PCR demonstrated fisetin-induced downregulation of proliferation-associated genes while promoting apoptotic gene expression. Molecular docking confirmed strong binding affinities between fisetin and mTOR signalling proteins, suggesting interference with oncogenic pathways.
Conclusion:
Fisetin exhibits potent cytotoxic and anti-proliferative effects in HSC-3 cells, modulating mTOR signalling. These findings support its potential as a therapeutic agent against oral carcinoma, warranting further