Acta Pharmacologica Sinica 2008 December; 29 (12): 1459-1466; doi: 10.1111/j.1745-7254.2008.00906.x

Acta Pharmacologica Sinica 2008 December; 29 (12): 1459-1466; doi: 10.1111/j.1745-7254.2008.00906.x

Original Article

Suberoyl bis-hydroxamic acid induces p53-dependent apoptosis of MCF-7 breast cancer cells¹

Zhi-gang ZHUANG^2,3, Fei FEI^2,4, Ying CHEN^2,4, Wei JIN^4,5

³Department of Breast Surgery, Shanghai First Maternity and Infant Health Hospital, Tongji University, Shanghai 200040, China; ⁴Department of Breast Surgery, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, China

Aim: To study the effects of suberoyl bis-hydroxamic acid (SBHA), an inhibitor of histone deacetylases, on the apoptosis of MCF-7 breast cancer cells.

Methods: Apoptosis in MCF-7 cells induced by SBHA was demonstrated by flow cytometric analysis, morphological observation, and DNA ladder. Mitochondrial membrane potential (ΔΨm) was measured using the fluorescent probe JC-1. The expressions of p53, p21, Bax, and PUMA were determined using RT-PCR or Western blotting analysis after the MCF-7 cells were treated with SBHA or p53 siRNA.

Results: SBHA induced apoptosis in MCF-7 cells. The expressions of p53, p21, Bax, and PUMA were induced, and ΔΨm collapsed after treatment with SBHA. p53 siRNA abrogated the SBHA-induced apoptosis and the expressions of p53, p21, Bax, and PUMA.

Conclusion: The activation of the p53 pathway is involved in SBHA-induced apoptosis in MCF-7 cells.

Keywords: suberoyl bis-hydroxamic acid; apoptosis; p53 pathway

¹This work was supported by the grant from the National Natural Science Foundation of China (No 30200151) and the Shanghai Pujiang Program and Innovation Program of Shanghai Municipal Education Commission (No 09ZZ04).

²These authors contributed equally to the present study.
⁵Correspondence to Prof Wei JIN.
Phn 86-21-6417-5590, ext 3422.
Fax 86-21-6443-4556.
E-mail jinwei7207@hotmail.com
Received 2008-05-31 Accepted 2008-09-27

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