Abstract
BackgroundSuberoyl bis-hydroxamic acid (SBHA) is a histone deacetylase (HDAC) inhibitor and exerts anti-growth effects in several malignancies including breast cancer. Proteasome inhibitors such as Bortezomib and MG-132 constitute novel anticancer agents. In this study, we investigated the synergistic antitumour activity of SBHA in combination with proteasome inhibitors.MethodsMCF-7 and MDA-MB-231 breast cancer cells were treated with SBHA, Bortezomib, and MG-132 alone or in combination for 72 h. Cell proliferation, colony formation, apoptosis and gene expression changes were examined.ResultsSBHA, Bortezomib, and MG-132 alone significantly inhibited the proliferation and colony formation and induced apoptosis in MCF-7 and MDA-MB-231 cells. Combined treatment showed a good synergistic antitumour effect against breast cancer cells. The p53 protein level was significantly elevated by combined treatment with SBHA and proteasome inhibitors. Moreover, combined treatment increased the expression of Bax, Bcl-xS, and Bak and decreased the expression of Bcl-2. Combination of SBHA with proteasome inhibitors causes synergistic anticancer effects on breast cancer cells. The potential molecular mechanism may involve induction of p53 and modulation of the Bcl-2 family proteins.ConclusionThese findings warrant further investigation of the therapeutic benefits of combination of SBHA with proteasome inhibitors in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-014-0107-7) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer is one of the most common malignant diseases affecting females worldwide, with more than 450,000 deaths each year [1]
Twenty-four hours after plating, cells were treated with Suberoyl bis-hydroxamic acid (SBHA) (40 μM), Bortezomib (5 nM), and MG-132 (250 nM), alone or in combination, for 72 h and examined for cell proliferation, apoptosis and gene expression changes
Combination of SBHA and proteasome inhibitors inhibits cell viability and colony formation of breast cancer cells WST-8 assay demonstrated that SBHA treatment for 72 h significantly (P
Summary
Breast cancer is one of the most common malignant diseases affecting females worldwide, with more than 450,000 deaths each year [1]. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to play an opposite role in the regulation of global gene expression via an epigenetic. Proteasome inhibitors such as Bortezomib and MG-132 constitute novel anticancer agents [9]. Combined treatment with HDAC inhibitors and proteasome inhibitors has been reported to enhance anticancer effects compared to each reagent alone [13,14]. Suberoyl bis-hydroxamic acid (SBHA) is a histone deacetylase (HDAC) inhibitor and exerts anti-growth effects in several malignancies including breast cancer. Proteasome inhibitors such as Bortezomib and MG-132 constitute novel anticancer agents. We investigated the synergistic antitumour activity of SBHA in combination with proteasome inhibitors
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