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

The apoptosis-inducing properties of RRR-alpha-, beta-, gamma-, and delta-t ocopherols, alpha-, gamma-, and delta-tocotrienol RRR-alpha-tocopheryl acet ate (vitamin E acetate), and RRR-alpha-tocopheryl succinate (vitamin E succ inate) were investigated in estrogen-responsive MCF7 and estrogen-nonrespon sive MDA-MB-435 human breast cancer cell lines in culture. Apoptosis was ch aracterized by two criteria: 1) morphology of 4,6-diamidino-2-phenylindole- stained cells and oligonucleosomal DNA laddering. Vitamin E succinate, a kn own inducer of apoptosis in several cell lines, including human breast canc er cells, sewed as a positive control. The estrogen-responsive MCF7 cells w ere more susceptible than the estrogen-nonresponsive MDA-MB-435 cells, with concentrations for half-maximal response for tocotrienols (alpha, gamma, a nd delta) and RRR-delta-tocopherol of 14, 15, 7, and 97 mu g/ml, respective ly. The tocotrienols (alpha, gamma, and delta) and RRR-delta-tocopherol ind uced MDA-MB-435 cells to undergo apoptosis, with concentrations for half-ma ximal response of 176, 28, 13, and 145 mu g/ml, respectively With the excep tion of RRR-delta-tocopherol, the tocopherols (alpha, beta, and gamma) and the acetate derivative of RRR-alpha-tocopherol (RRR-alpha-tocopheryl acetat e) were ineffective in induction of apoptosis in both cell lines when teste d within the range of their solubility, i.e., 10-200 mu g/ml. In summary, t hese studies demonstrate that naturally occurring tocotrienols and RRR-delt a-tocopherol are effective apoptotic inducers for human breast cancer cells .