[Synergistic antitumor effect of sodium caffeate and mitomycin].
OBJECTIVE
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 s.c. 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, i.p., x 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.


CONCLUSIONS
The combination of CA-Na and MMC showed synergistic effect against tumor cell proliferation in vitro and tumor growth in vivo.
Xu
Feng
F
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Song
Dan-qing
DQ
Zhen
Yong-su
YS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002109:Caffeic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D016685:Mitomycin; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002118:Calcium; C040048:caffeic acid