The Antiproliferative Effects Of Resveratrol Derivatives And Their Mechanisms Of Actions In Cancer Cells

Cell growth inhibitory effects of ten resveratrol (RES) derivatives were investigated in human leukemia and breast cancer cells using the trypan blue exclusion assay and the MTT assay and revealed that compound Bn was the most potent one. The mechanisms of action of Bn in inhibiting cell growth were explored and compared with that of RES in human leukemia HL-60 and K562 cells. Both Bn and RES induced apoptosis in HL-60 cells. Bn exhibited apoptosis induction at a concentration of 1.6μM, but 40μM of RES was required to induce evident apoptosis as determined by morphologica changes, sub-G1 induction and PARP cleavage. Bn and RES induced the production of H2O2 and decrease in the levels of mitochondrial membrane potential suggesting that an intrinsic apoptotic pathway maybe involved in Bn and RES-induced apoptosis in HL-60 cells. Both Bn and RES induced the activation of caspase-8, suggesting that an extrinsic apoptotic pathway is involved in Bn and RES-induced apoptosis in HL-60 cells. Although Bn induced cytotoxicity in K562 cells but apoptotic cells were not detected. Cells in sub-G1 phase only occurred after treatment at higher concentrations or prolonged times. Bn, but not RES, induced G2/M arrest in K562 cells and Western blot analysis revealed that the levels of cyclin B1, P21 and Servivin protein were upregulated. These results suggest that Bn induce cell death in K562 cells through induction of mitotic catastrophe. Similar to K562 cells, breast cancer cells were responsive to Bn treatment with the induction of G2/M phase. The novel mechanism of Bn in inducing mitotic catastrophe and/or apoptosis implies that it could be developed as a new agent for the treatment of cancer.