Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells
Joint Authors
Malaviya, Abhita
Sylvester, Paul W.
Source
International Journal of Breast Cancer
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-01-28
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
γ-Tocotrienol is a natural vitamin E that displays potent anticancer activity, and previous studies suggest that these effects involve alterations in PPARγ activity.
Treatment with 0.5–6 μM γ-tocotrienol, 0.4–50 μM PPARγ agonists (rosiglitazone or troglitazone), or 0.4–25 μM PPARγ antagonists (GW9662 or T0070907) alone resulted in a dose-responsive inhibition of MCF-7 and MDA-MB-231 breast cancer proliferation.
However, combined treatment of 1–4 μM γ-tocotrienol with PPARγ agonists reversed the growth inhibitory effects of γ-tocotrienol, whereas combined treatment of 1–4 μM γ-tocotrienol with PPARγ antagonists synergistically inhibited MCF-7 and MDA-MB-231 cell growth.
Combined treatment of γ-tocotrienol and PPARγ agonists caused an increase in transcription activity of PPARγ along with increased expression of PPARγ and RXR, and decrease in PPARγ coactivators, CBP p/300, CBP C-20, and SRC-1, in both breast cancer cell lines.
In contrast, combined treatment of γ-tocotrienol with PPARγ antagonists resulted in a decrease in transcription activity of PPARγ, along with decreased expression of PPARγ and RXR, increase in PPARγ coactivators, and corresponding decrease in PI3K/Akt mitogenic signaling in these cells.
These findings suggest that elevations in PPARγ are correlated with increased breast cancer growth and survival, and treatment that decreases PPARγ expression may provide benefit in the treatment of breast cancer.
American Psychological Association (APA)
Malaviya, Abhita& Sylvester, Paul W.. 2013. Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells. International Journal of Breast Cancer،Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-446395
Modern Language Association (MLA)
Malaviya, Abhita& Sylvester, Paul W.. Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells. International Journal of Breast Cancer No. 2013 (2013), pp.1-17.
https://search.emarefa.net/detail/BIM-446395
American Medical Association (AMA)
Malaviya, Abhita& Sylvester, Paul W.. Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells. International Journal of Breast Cancer. 2013. Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-446395
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-446395