Suberoyl bis-hydroxamic acid enhances cytotoxicity induced by proteasome inhibitors in breast cancer cells.
BACKGROUND
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. In this study, we investigated the synergistic antitumour activity of SBHA in combination with proteasome inhibitors.


METHODS
MCF-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.


RESULTS
SBHA, 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.


CONCLUSIONS
These findings warrant further investigation of the therapeutic benefits of combination of SBHA with proteasome inhibitors in breast cancer.
Department of Radiation Oncology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Xuhui District Shanghai, 200233 China.
Xinmiao
X
Yang
Department of Radiation Oncology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Xuhui District Shanghai, 200233 China.
Zeliang
Z
Shi
Department of Medical Oncology, Minhang Branch of Fudan, University Shanghai Cancer Center, Shanghai, China.
Ning
N
Zhang
Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Fudan University, Shanghai, China.
Zhouluo
Z
Ou
Department of Radiation Oncology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Xuhui District Shanghai, 200233 China.
Shen
S
Fu
Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.
Xichun
X
Hu
Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Fudan University, Shanghai, China.
Zhenzhou
Z
Shen
Anticancer therapy; Bcl-2 family; Histone deacetylase; Proteasome inhibition; Synergism