3,3′,4′,5′-Tetramethoxychalcone Inhibits Human Oral Cancer Cell Proliferation and Migration via p53-mediated Mitochondrial-dependent Apoptosis

Background/Aim: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). Materials and Methods: The effect of 3,3',4',5' -tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Results: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 mu M) by inducing G(2)/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of hi stone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2-associated x protein, while reducing the mitochondrial membrane potential, and expression of B-cell lymphoma-2. In addition, TMC reduced the migration potential of OSCC cells by attenuating the C-C chemokine ligand 5/C-C chemokine receptor type 5 axis. Conclusion: These data indicate that TMC may be considered an interesting target for further development of chemotherapeutic agents against oral cancer.