Send to

Choose Destination
Biochem Cell Biol. 2015 Aug;93(4):306-20. doi: 10.1139/bcb-2014-0123. Epub 2015 Mar 12.

γ-Tocotrienol-induced endoplasmic reticulum stress and autophagy act concurrently to promote breast cancer cell death.

Author information

School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA.


The anticancer effects of γ-tocotrienol are associated with the induction of autophagy and endoplasmic reticulum (ER) stress-mediated apoptosis, but a direct relationship between these events has not been established. Treatment with 40 μmol/L of γ-tocotrienol caused a time-dependent decrease in cancer cell viability that corresponds to a concurrent increase in autophagic and endoplasmic reticulum (ER) stress markers in MCF-7 and MDA-MB-231 human breast cancer cells. γ-Tocotrienol treatment was found to cause a time-dependent increase in early phase (Beclin-1, LC3B-II) and late phase (LAMP-1 and cathepsin-D) autophagy markers, and pretreatment with autophagy inhibitors Beclin-1 siRNA, 3-MA or Baf1 blocked these effects. Furthermore, blockage of γ-tocotrienol-induced autophagy with Beclin-1 siRNA, 3-MA, or Baf1 induced a modest, but significant, reduction in γ-tocotrienol-induced cytotoxicity. γ-Tocotrienol treatment was also found to cause a decrease in mitogenic Erk1/2 signaling, an increase in stress-dependent p38 and JNK1/2 signaling, as well as an increase in ER stress apoptotic markers, including phospho-PERK, phospho-eIF2α, Bip, IRE1α, ATF-4, CHOP, and TRB3. In summary, these finding demonstrate that γ-tocotrienol-induced ER stress and autophagy occur concurrently, and together act to promote human breast cancer cell death.


apoptose; apoptosis; autophagie; autophagy; breast cancer; cancer du sein; endoplasmic reticulum stress; stress du réticulum endoplasmique; γ-tocotrienol; γ-tocotriénol

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center