β-Carotene and/or vitamin E as modulators of alkylating agents in SCC-25 human squamous carcinoma cells

Dietary levels of β-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of β-carotene, vitamin E, and the combination of β-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. β-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. β-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both β-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with β-carotene (70 μm, 2h) resultec in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of β-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%–45% over the control value. Treatment with β-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human karotinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of β-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.