Synergistic antitumor effect of sodium caffeate and mitomycin

AIM To study the synergistic antitumor effect of sodium caffeate (sodium 3,4 dihydroxycinnamate, CA Na) and mitomycin C (MMC). METHODS MTT assay, Western Blotting analysis and flow cytometry were used to determine the effects of MMC alone and in combination with CA Na on tumor cell proliferation, cell cycle progression and the expression of apoptosis involved proteins Bcl 2 and caspase 3. Intracellular Ca 2+ level and mitochondria membrane potential were also assayed. Inhibition of tumor growth was evaluated with hepatoma 22 transplanted sc in mice. RESULTS Synergistic inhibition of hepatoma BEL 7402 cell proliferation was achieved by the combination of MMC and CA Na. The combination of MMC and CA Na caused more remarkable cell cycle perturbation in BEL 7402 cells than MMC alone. Combination of CA Na and MMC synergistically inhibited Bcl 2 expression and enhanced caspase 3 expression of the cells. Intracellular Ca 2+ level was significantly increased when the cells were treated with MMC combined with CA Na. Mitochondria membrane potential was markedly decreased when treated with the combination. At doses of 0 5 , 1 0 and 1 5 mg·kg -1 , ip, ×10, MMC inhibited the growth of hepatoma 22 by 35 9%, 62 7% and 79 1%, respectively. In combination with CA Na, the inhibition rates of MMC increased to 62 4%, 70 5% and 88 0%, respectively. CONCLUSION The combination of CA Na and MMC showed synergistic effect against tumor cell proliferation in vitro and tumor growth in vivo .