Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells.
Mol Carcinog
; 52(5): 404-11, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-22290509
ABSTRACT
Breast cancer patients with HER-2 positive or estrogen receptor negative tumors have a poor prognosis because these tumors are aggressive and respond poorly to standard therapies. Histone deacetylase (HDAC) inhibitors have been shown to decreased cell survival, which suggests that HDAC inhibitors may be developed for preventing and treating breast cancer. Curcumin has anti-inflammatory and proapoptotic effects in cancer cells. We determined whether the HDAC inhibitor, Tricostatin A (TSA) in combination with curcumin would produce greater antiproliferative and apoptotic effects than either agent alone. Increasing the concentration of curcumin from 10 to 20 µM enhanced the growth inhibitory effects of the combination in SkBr3 and 435eB breast cancer cells, which was accompanied by decreased viability along with decreased phosphorylation of ERK and Akt. The decreased cell viability observed in SkBr3 cells when curcumin was combined with TSA led to a G0/G1 cell cycle arrest and increased p21 and p27, and decreased Cyclin D1 protein expression. The combination induced cleavage of caspase 3 and poly(ADP-ribose) polymerase-1, suggesting that cell death occurred by apoptosis. There were no changes in protein expression of Bcl2, Bax, or Bcl-xL and decreased expression of p53. The combination increased protein expression of phosphorylated JNK and phosphorylated p38. Pharmacological inhibition of JNK, but not p38, attenuated the decreased viability induced by the curcumin and TSA combination. We conclude that p53 independent apoptosis induced by combining curcumin and TSA involves JNK activation. These findings provide a rationale for exploring the potential benefits of the combination of curcumin with TSA for treatment of breast cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
/
Curcumin
/
Hydroxamic Acids
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country: