Potentiated antitumor effects of butyrate and actinomycin D in melanoma model in mice

Butyrate and butyric acid derivatives are well known to induce differentiation and apoptosis of tumor cells and have also recently gained acceptance as potential anticancer agents. In this study we observed an increased expression of mTNFα in tumor tissues in mice treated with butyrate prodrug tributyrin. Since in in vitro experiments we observed a potentiating effects of TNFa and actinomycin D on B16F10 cells and also a synergistic interaction was previously claimed between those agents, we investigated the anti-tumor activity of the combination therapy with butyrate and actinomycin D in the B16F10 melanoma model in mice. The combination of the drugs resulted in a strongly potentiated tumor growth retardation in melanoma bearing mice. However the B16F10 cells in vitro did not produce any detectable amounts of TNFa. The presented data strongly suggest that one of the mechanism of this successful drug combination could depend on the interaction of the actinomycin D with butyrate-induced TNFa produced by stromal or tumor infiltrating immune cells. The results illustrate also the possible application of this combination in cancer therapy.