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

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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.

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Abbreviations

CI:

Combination index

DRI:

Dose reduction index

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 21072105) and the Independent Innovation Foundation of Shandong University (No.2009DX002).

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Authors and Affiliations

  1. National Glycoengineering Research Center, Shandong University, No. 44 West Wenhua Road, Jinan, China

    Yi-kang Shi, Xi-qian Han & Feng-shan Wang

  2. College of Pharmacy, Nankai University and the Key Laboratory of Molecular Pharmacy of Tianjin City, Tianjin, China

    Zhong-hua Li, Zhen-hua Wang, Jing-li Hou, Cong-ran Feng, Qing-hong Fang, Hui-hui Wang, Peng-fei Zhang, Jie Shen & Peng Wang

  3. Shandong Academy of Occupational Health and Occupational Medicine, No. 89, Jingshi Road, Jinan, China

    Ji-hu Yi

  4. Departments of Biochemistry and Chemistry, The Ohio State University, Columbus, OH, 43210, USA

    Peng Wang

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  1. Yi-kang Shi
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Correspondence to Yi-kang Shi.

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Shi, Yk., Li, Zh., Han, Xq. et al. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances taxol-induced cell death in breast cancer. Cancer Chemother Pharmacol 66, 1131–1140 (2010). https://doi.org/10.1007/s00280-010-1455-1

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  • DOI: https://doi.org/10.1007/s00280-010-1455-1

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