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

Abstract

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 micrograms/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 micrograms/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 micrograms/ml. In summary, these studies demonstrate that naturally occurring tocotrienols and RRR-delta-tocopherol are effective apoptotic inducers for human breast cancer cells.

• Authors: W Yu, M Simmons-Menchaca, A Gapor, B G Sanders, K Kline
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 33 Issue 1 Pg. 26-32 ( 1999) ISSN: 0163-5581 [Print] United States
• PMID: 10227040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Chromans
• Chromatin
• DNA, Neoplasm
• Tocotrienols
• Vitamin E
• tocotrienol, delta
• plastochromanol 8
• tocotrienol, beta
• tocotrienol, alpha

Topics

• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (pathology)
• Chromans (pharmacology)
• Chromatin (drug effects)
• DNA, Neoplasm (biosynthesis, drug effects)
• Female
• Humans
• Neoplasms, Hormone-Dependent (pathology)
• Tocotrienols
• Tumor Cells, Cultured (drug effects)
• Vitamin E (analogs & derivatives, pharmacology)