Cells: A Possible Role for Glutathione and Adriamycin in Caco-2 Human Colon Adenocarcinoma Biochemical Characterization of Resistance to Mitoxantrone

Cytotoxicity of Adriamycin on human colon adenocarcinoma cell lines was investigated. Concentrations of Adriamycin producing 50% inhibition were very similar in HT29, Sw480, Sw620, and Swl 116 cells, whereas Caco-2 cells were relatively insensitive. As compared to the Swl 116 cell line, Caco-2 cells were also insensitive to mitoxantrone. Sensitivity to cisplatin, 5-fluorouracil, or ethacrynic acid was comparable in both cell lines. To find the mechanism for this mitoxantrone and Adriamycin resistance, several potential Adriamycin-detoxifying systems were char acterized and quantified in both Swlllo and Caco-2 cells. No dramatic differences in glutathione content and expression of both selenium de pendentand independent glutathione peroxidase, UDP-glucuronyltransferase, and cytochrome P-450 were found. However, highly significant differences in glutathione 5-transferase activity were present, the expres sion of both class ir and class a glutathione S-transferases being much higher in the Caco-2 cell line. In addition, a slightly higher content of P170 glycoprotein was present in the Caco-2 cells. These findings suggest that glutathione 5-transferases, and to a lesser extent the P-170 glyco protein, may be involved in mitoxantrone and Adriamycin resistance of Caco-2 colon carcinoma cells.