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 Ca²⁺ 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 Ca²⁺ 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.