The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances taxol-induced cell death in breast cancer.

Abstract

PURPOSE:

The histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) enhances taxol-induced antitumor effects against some human cancer cells. The aim of this study is to investigate whether SAHA can enhance taxol-induced cell death against human breast cancer cells and to illustrate the mechanism in detail.

METHODS:

A panel of eight human breast cancer cell lines and an immortalized human breast epithelial cell line were used to determine the inhibitory effects of SAHA, taxol, or their combination by MTT assay. The effects of SAHA with or without taxol on cell cycle distributions, apoptosis, and protein expressions were also examined. The inhibitory effects on tumor growth were characterized in vivo in BALB/c nude mice bearing a breast cancer xenograft model.

RESULTS:

Taxol-resistant and multi-resistant breast cancer cells were as sensitive to SAHA as taxol-sensitive breast cancer cells. A dose-dependent synergistic growth inhibition was found in all the tested breast cancer cell lines treated with the SAHA/taxol combinations. The synergetic effect was also observed in the in vivo xenograft tumor model. The cell cycle analysis and apoptosis assay showed that the synergistic effects resulted from enhanced G2/M arrest and apoptosis.

CONCLUSIONS:

SAHA increased the anti-tumor effects of taxol in breast cancer in vitro and in vivo. The combination of SAHA and taxol may have therapeutic potential in the treatment of breast cancer.

• Authors: Yi-kang Shi, Zhong-hua Li, Xi-qian Han, Ji-hu Yi, Zhen-hua Wang, Jing-li Hou, Cong-ran Feng, Qing-hong Fang, Hui-hui Wang, Peng-fei Zhang, Feng-shan Wang, Jie Shen, Peng Wang
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 66 Issue 6 Pg. 1131-40 (Nov 2010) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20838997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Vorinostat
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• Drug Synergism
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Hydroxamic Acids (pharmacology)
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Paclitaxel (pharmacology)
• Transplantation, Heterologous
• Vorinostat