Abstract
Epidemiological studies have highlighted the ability of phytochemicals to reduce the
risk of breast cancer by attenuating specific intracellular signaling pathways that
regulate cell proliferation and survival. γ-Tocotrienol is a natural form of vitamin E that displays potent anticancer activity
at doses that have no discernible toxicity toward normal cells. Sesamin is an abundant
phytochemical found in sesame seed oil that also shows antiproliferative and antiangiogenic
activity against human breast cancer cells. In this study, the combined treatment
of subeffective doses of γ-tocotrienol and sesamin caused a synergistic inhibition of murine +SA mammary epithelial
cell growth, as determined by the MTT assay and immunofluorescent Ki-67 staining.
Western blot studies revealed that combined low-dose treatment of γ-tocotrienol and sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4
receptors phosphorylation (activation) and a relatively large decrease in intracellular
levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p-NFκB, Jak1, Jak2, and Stat1, as compared to cells treated with only one compound or in
the vehicle-treated control group. These findings demonstrate that the synergistic
growth inhibitory effects of γ-tocotrienol and sesamin treatment are associated with suppression of EGF-dependent
mitogenic signaling in mammary tumor cells and suggest that dietary supplementation
with these phytochemicals may provide some benefits in the prevention and/or treatment
of breast cancer.
Key words
γ-tocotrienol - sesamin - ErbB receptors - phytochemicals - breast cancer
