Cytotoxic activity of fusaric acid on human adenocarcinoma cells in tissue culture.

When cultured human normal WI-38 fibroblasts were exposed to 500 microM fusaric acid (5-butylpicolinic acid), cell proliferation ceases. The majority of the WI-38 cells remained in a quiescent G1(G0) state and viable for approximately 30 to 48 h. The effect of fusaric acid on WI-38 cell growth was slowly reversible after removal of the agent from the culture media. In contrast, within 24 h of exposure to 500 microM fusaric acid, most of the human colon adenocarcinoma LoVo cells were blocked at random in the cell cycle and approximately 80% of the cells were dead after 30 h. Three additional human colorectal adenocarcinoma cell lines, denoted SW48, SW480, and SW742, were also sensitive to the inhibitory and cytotoxic effects of fusaric acid. Of all the cell lines tested, the human mammary adenocarcinoma cell line MDA-MB-468 was the most sensitive to the growth inhibitory and cytotoxic effects of fusaric acid. Further experiments with MDA-MB-468 cells demonstrated that fusaric acid is a potent inhibitor of DNA synthesis. Fusaric acid also inhibited the growth of human epidermoid carcinoma KB cells and showed cytotoxic actions for this cell line but its effects on cell viability were not as pronounced. The results presented here indicate that fusaric acid has potent anti-proliferative activity in vitro on various normal and cancer cell lines and suggest that it exhibits some cytotoxic specificity for growing and confluent colorectal adenocarcinoma and mammary adenocarcinoma cell lines.