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

Abstract

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 (DeltaPsim) 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 DeltaPsim 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.

• Authors: Zhi-gang Zhuang, Fei Fei, Ying Chen, Wei Jin
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 12 Pg. 1459-66 (Dec 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 19026165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BAX protein, human
• BBC3 protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Proto-Oncogene Proteins
• RNA, Small Interfering
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• suberoyl bis-hydroxamic acid

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Breast Neoplasms (metabolism)
• Cell Line, Tumor (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Female
• Histone Deacetylase Inhibitors
• Humans
• Hydroxamic Acids (pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Proto-Oncogene Proteins (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)