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

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

Volume 16, 12 Issues, 2016

Download PDF Flyer

Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

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

Anti-Cancer Agents in Medicinal Chemistry, 13(7): 1039-1047.

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

Affiliation: College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Monroe, LA 71209-0470, USA.


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.


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

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 13
Issue Number: 7
First Page: 1039
Last Page: 1047
Page Count: 9
DOI: 10.2174/18715206113139990116
Price: $58

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science