Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols

• Published in: Nutrition and cancer 1999, Vol.33 (1), p.26-32
• Main Authors: Yu, W, Simmons-Menchaca, M, Gapor, A, Sanders, B.G, Kline, K
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; apoptosis; Apoptosis - drug effects; Biological and medical sciences; breast neoplasms; Breast Neoplasms - pathology; Carcinogenesis, carcinogens and anticarcinogens; cell lines; Chromans - pharmacology; Chromatin - drug effects; DNA, Neoplasm - biosynthesis; DNA, Neoplasm - drug effects; Female; Foods and miscellaneous; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Neoplasms, Hormone-Dependent - pathology; tocopherols; tocopheryl succinate; Tocotrienols; Tumor Cells, Cultured - drug effects; Tumors; Vitamin E - analogs & derivatives; Vitamin E - pharmacology; vitamin e acetate
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635589909514744

The apoptosis-inducing properties of RRR-alpha-,beta-, gamma-, and delta-tocopherols, alpha-, gamma-, and delta-tocotrienols, RRR-alpha-tocopheryl acetate (vitamin E acetate), and RRR-alpha-tocopheryl succinate (vitamin E succinate) were investigated in estrogen-responsive MCF7 and estrogen-nonresponsive MDA-MB-435 human breast cancer cell lines in culture. Apoptosis was characterized by two criteria: 1) morphology of 4,6-diamidino-2-phenylindole-stained cells and oligonucleosomal DNA laddering. Vitamin E succinate, a known inducer of apoptosis in several cell lines, including human breast cancer cells, served as a positive control. The estrogen-responsive MCF7 cells were more susceptible than the estrogen-nonresponsive MDA-MB-435 cells, with concentrations for half maximal response for tocotrienols (alpha, gamma, and delta and RRR-delta-tocopherol of 14, 15, 7, and 97 microgram/ml, respectively. The tocotrienols (alpha, gamma, and delta) and RRR-delta-tocopherol induced MDA-MB-435 cells to undergo apoptosis, with concentrations for half-maximal response of 176, 28, 13, and 145 microgram/ml, respectively. With the exception of RRR-delta-tocopherol, the tocopherols (alpha, beta, and gamma) and the acetate derivative of RRR-alpha-tocopherol (RRR-alpha-tocopheryl acetate) were ineffective in induction of apoptosis in both cell lines when tested within the range of their solubility, i.e., 10-200 microgram/ml. In summary, these studies demonstrate that naturally occurring tocotrienols and RRR-delta-tocopherol are effective apoptotic inducers for human breast cancer cells.