The selective cytotoxic effect of carotenoids and alpha-tocopherol on human cancer cell lines in vitro.
This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.
Schwartz
J
J
Department of Oral Pathology, Harvard School of Dental Medicine, Boston, MA 02115.
Shklar
G
G
D001943:Breast Neoplasms; D016644:Canthaxanthin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry; D002338:Carotenoids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008175:Lung Neoplasms; D008544:Melanocytes / Q000187:drug effects; D008545:Melanoma / Q000737:chemistry; D009062:Mouth Neoplasms / Q000737:chemistry; D009363:Neoplasm Proteins / Q000032:analysis; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene
D009363:Neoplasm Proteins; D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; D016644:Canthaxanthin; D013385:Succinate Dehydrogenase