Beta-carotene and/or vitamin E as modulators of alkylating agents in SCC-25 human squamous carcinoma cells.
Dietary levels of beta-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 beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-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. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted 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 beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.
Schwartz
J L
JL
Harvard School of Dental Medicine, Department of Oral Pathology, Boston, MA.
Tanaka
J
J
Khandekar
V
V
Herman
T S
TS
Teicher
B A
BA
D000477:Alkylating Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D002338:Carotenoids / Q000494:pharmacology*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008558:Melphalan / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D019207:beta Carotene; D014810:Vitamin E; C055423:didimethylsulfoxide dichloroplatinum(II); D002338:Carotenoids; D008558:Melphalan