Synergistic Effects of Combined Treatment with Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid and TRAIL on Human Breast Cancer Cells

Funding Source

National Natural Science Foundation of China, Shenyang Science and Technology Bureau

Grant Number

2014020128, 2G12MD007595, 81172509, F15-199-1-28


Department of Chemistry

Document Type


Publication Date



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.


DOI: 10.1038/srep28004

PubMed ID: 27292433

Funding text

The work is supported by the National Natural Science Foundation of China (81172509), the Research Foundation of Science and Technology Department of Liaoning Province (2014020128), the Research Foundation of Shenyang Science and Technology Bureau (F15-199-1-28), RCMI Cancer Research Center through an NIH grant 2G12MD007595.