Garcinol, a natural benzophenone overcomes radio and chemoresistance by targeting PI3K-PKB/AKT pathway in rhabdomyosarcoma cells.

AKT signaling pathway is a critical intracellular signaling pathway involved in regulating various cellular processes, including cell proliferation, cell survival, cell migration and metabolism. Cancer cells have a propensity to alter the expression of pro- and anti-angiogenic signals to activate the angiogenic switch. Aberrant overexpression of AKT pathway is associated with various types of cancers and enables the migration and invasion of tumor cells to neighboring tissues. Garcinol, a natural benzophenone, displays potent anticancer potential against various cancer cells, but its mechanism of action in inducing apoptosis remains unclear. The present study aimed to unveil the mechanism of action of garcinol in inducing apoptosis in rhabdomyosarcoma cells. Garcinol inhibited cell proliferation, reduced the viability of cancer cells, diminished colony formation, and mitigated the migratory capabilities of Rh cells. In vitro analysis of garcinol unveiled potent anticancer and anti-metastatic activity, with an IC50 ranging from 5.32 to 16.28 against Rh cell lines, as demonstrated by MTT assay. Garcinol actuates apoptosis by triggering mitotic arrest (G2/M phase arrest) in Rh cell lines and alters the expression of pro-apoptotic and anti-apoptotic proteins to trigger efficient apoptosis in cancer cells.