| Autor: |
Tiwari RV; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA.; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA., Parajuli P; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA.; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA., Sylvester PW; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA.; School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe LA 71209, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2015 Aug; Vol. 93 (4), pp. 306-20. Date of Electronic Publication: 2015 Mar 12. |
| DOI: |
10.1139/bcb-2014-0123 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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