Gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant
phenol, showed selective cytotoxicity against
tumor cells with higher sensitivity than normal cells such as hepatocytes and keratinocytes. To elucidate the difference in sensitivity between normal and
tumor cells to
gallic acid, we studied whether the inhibitor of
gallic acid-induced apoptosis existed or not. A serum-free
conditioned medium, prepared from high density rat primary cultured hepatocytes and cytoplasm of hepatocytes, prevented
gallic acid-induced apoptosis. In contrast,
hepatomas and hepatic cell lines such as dRLh-84, PLC/PRF/5, HLE, and HUH and two other kinds of
tumor cell, HeLa and KB, scarcely generated such an inhibitor in either their
conditioned medium or their cells. Biochemical characterization of the inhibitors revealed that the inhibitor in the hepatocyte
conditioned medium was completely inactivated by heating at 65 degrees C for 10 min. Its molecular weight was estimated at 150-250 kDa by gel filtration column chromatography, indicating that the inhibitor may be a
protein-like substance. These results suggest that the generation of a large amount of the inhibitor may endow hepatocytes with insensitivity to
gallic acid. In conclusion, the difference in the amount of the inhibitors generated by hepatocytes and
tumor cells should contribute to the underlying mechanism in the difference in sensitivity of cells to
gallic acid.