Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells.
Previous studies showed that either histone deacetylase (HDAC) inhibitors or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in tumor cells including breast cancer. However, the underling mechanisms of combining HDAC inhibitors with TRAIL in the treatment of breast cancer are poorly understood. In this study, we determined the ability of SAHA and TRAIL as single agents or in combination to inhibit the growth and survival of MCF-7 and MDA-MB-231 breast cancer cells. Our results demonstrate that the distinct effects of SAHA or TRAIL individually and in combination on the proliferation, cell viability, apoptosis, cell cycle distribution, and morphological changes of MDA-MB-231 and MCF-7 cells. We further determined the different effects of SAHA or TRAIL alone and combining SAHA with TRAIL on the expression of a number of apoptosis-related molecules, cell cycle, growth factors and their receptors in cancer cells. Our results demonstrated that the combinatorial treatment of SAHA and TRAIL may target multiple pathways and serve as an effective therapeutic strategy against breast cancer. An improved understanding of the molecular mechanisms may facilitate either SAHA or TRAIL targeted use and the selection of suitable combinations.
Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, No. 146 North Huanghe St, Huanggu Dis, Shenyang City, Liaoning Pro 110034, P. R. China.
Weiqiang
W
Zhou
Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, No. 146 North Huanghe St, Huanggu Dis, Shenyang City, Liaoning Pro 110034, P. R. China.|The Second Affiliated Hospital of Shenyang Medical College, No. 20 North 9th St, Heping Dis, Shenyang City, Liaoning Pro 110002, P. R. China.
Xiuyan
X
Feng
Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, No. 146 North Huanghe St, Huanggu Dis, Shenyang City, Liaoning Pro 110034, P. R. China.
Han Han
RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA.|Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Shanchun
S
Guo
RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA.|Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Guangdi
G
Wang
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061986:MCF-7 Cells; D017978:Receptors, Growth Factor / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D000077337:Vorinostat
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D017978:Receptors, Growth Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; D000077337:Vorinostat