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

Abstract

The apoptosis‐inducing properties of RRR‐α‐, β‐, γ‐, and δ‐tocopherols, α‐, γ‐, and δ‐tocotrienols, RRR‐α‐tocopheryl acetate (vitamin E acetate), and RRR‐α‐tocopheryl succi‐nate (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‐diamid‐ino‐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 (α, γ, and δ) and RRR‐δ‐tocopherol of 14, 15, 7, and 97 μg/ml, respectively. The tocotrienols (α, γ, and δ) and RRR‐δ‐tocopherol induced MDA‐MB‐435 cells to undergo apoptosis, with concentrations for half‐maximal response of 176, 28, 13, and 145 μg/ml, respectively. With the exception of RRR‐δ‐tocopherol, the tocopherols (α, β, and γ) and the acetate derivative of RRR‐α‐tocopherol (RRR‐α‐tocopheryl acetate) were ineffective in induction of apoptosis in both cell lines when tested within the range of their solubility, i.e., 10–200 μg/ml. In summary, these studies demonstrate that naturally occurring tocotrienols and RRR‐δ‐tocopherol are effective apoptotic inducers for human breast cancer cells.