OBJECTIVE: The current research aimed to synthesize several Schiff base ligands from (3-formyl-4-hydroxyphenyl) methyltriphenylphosphonium (T). Additionally, the current research aimed to study the growth inhibitory effect of triphenylphosphonium containing thiosemicarbazone derivatives on PC-3 cells by deciphering the mechanisms involved in cell death.
METHOD: The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR, HRESIMS and X-ray crystallography) and the results were in conformity with the structure of the targeted compounds. Growth inhibitory effect of the compounds were performed against six human cell lines.
RESULTS: DM(tsc)T displayed most potent activity against PC-3 cells with IC50 value of 2.64 ± 0.33 μM, surpassing that of the positive control cisplatin (5.47 ± 0.06 μM). There were marked morphological changes observed in DM(tsc)T treated cells stained with acridine orange and ethidium bromide which were indicative of cell apoptosis. Treatment with DM(tsc)T showed that the cell cycle is arrested in the G0/G1 phase after 72 hours. Mitochondrial membrane potential loss was observed in cells treated with DM(tsc)T, indicating the apoptosis could be due to mitochondria mediated pathway.
CONCLUSION: This study indicates that DM(tsc)T would serve as a lead scaffold for rational anticancer agent development.
METHODS: Cell proliferation, migration, TUNEL assay, western blotting, time-lapse confocal microscopy analyses, chorioallantoic membrane assay, and a xenograft BALB/c nude mouse system were used in this study. Chemical fingerprinting of AC-3E was established using LC-MS.
RESULTS: AC-3E attenuated T47D breast cancer cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators, and inducing apoptosis. AC-3E also effectively inhibited tube-like structures of endothelial cells, blood vessel branching and microvessel formation ex vivo and in vivo. Significant preventive and therapeutic effects against T47D mammary tumor growth of AC-3E was observed comparable or superior to tamoxifen treatment in xenograft BALB/c nude mice. Dehydroeburicoic acid (2) was characterized as the main chemical constituent in AC-3E against breast cancer.
CONCLUSION: This study suggests that AC-3E extracts can be employed as a double-barreled approach to treat human ER+ breast cancer by attacking both cancer cells and tumor-associated blood vessel cells.