Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Tocotrienols Target PI3K/Akt Signaling in Anti-Breast Cancer Therapy

Author(s): Paul W. Sylvester and Nehad M. Ayoub

Volume 13, Issue 7, 2013

Page: [1039 - 1047] Pages: 9

DOI: 10.2174/18715206113139990116

Price: $65

Abstract

The PI3K/Akt signaling pathway mediates mitogen-dependent growth and survival in various types of cancer cells, and inhibition of this pathway results in tumor cell growth arrest and apoptosis. Tocotrienols are natural forms of vitamin E that displays potent anticancer activity at treatment doses that had little or no effect on normal cell viability. Mechanistic studies revealed that the anticancer effects of γ-tocotrienol were associated with a suppression in PI3K/Akt signaling. Additional studies showed that cytotoxic LD50 doses of γ-tocotrienol were 3-5-fold higher than growth inhibitory IC50 treatment doses, suggesting that cytotoxic and antiproliferative effects of γ-tocotrienol might be mediated through different mechanisms. However, γ-tocotrienol-induced caspase activation and apoptosis in mammary tumor cells was also found to be associated with suppression in intracellular PI3K/Akt signaling and subsequent down-regulation of FLIP, an endogenous inhibitor of caspase processing and activation. Since breast cancer cells are significantly more sensitive to the inhibitory effects of γ-tocotrienol on PI3K/Akt signaling than normal cells, these findings suggest that γ-tocotrienol may provide significant health benefits in reducing the risk of breast cancer in women. Studies have also shown that combined treatment of γ-tocotrienol with other chemotherapeutic agents can result in a synergistic anticancer response. Combination therapy was most effective when the anticancer mechanism of action of γ-tocotrienol is complimentary to that of the other drug and can provide significant health benefits in the prevention and/or treatment of breast cancer, while at the same time avoiding tumor resistance or toxic effects that is commonly associated with high dose monotherapy.

Keywords: Vitamin E, tocotrienols, PI3K, Akt, breast cancer.


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy