Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Enhances Radiosensitivity and Suppresses Lung Metastasis in Breast Cancer In Vitro and In Vivo

Hui Wen Chiu, Ya Ling Yeh, Yi Ching Wang, Wei Jan Huang, Yi An Chen, Yi Shiou Chiou, Sheng Yow Ho, Pinpin Lin, Ying Jan Wang

Research output: Contribution to journalArticle

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Abstract

Triple-negative breast cancer (TNBC), defined by the absence of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, is associated with an early recurrence of disease and poor outcome. Furthermore, the majority of deaths in breast cancer patients are from metastases instead of from primary tumors. In this study, MCF-7 (an estrogen receptor-positive human breast cancer cell line), MDA-MB-231 (a human TNBC cell line) and 4T1 (a mouse TNBC cell line) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with suberoylanilide hydroxamic acid (SAHA, an inhibitor of histone deacetylase (HDAC)) and to determine the underlying mechanisms of these effects in vitro and in vivo. We also evaluated the ability of SAHA to inhibit the metastasis of 4T1 cells. We found that IR combined with SAHA showed increased therapeutic efficacy when compared with either treatment alone in MCF-7, MDA-MB-231 and 4T1 cells. Moreover, the combined treatment enhanced DNA damage through the inhibition of DNA repair proteins. The combined treatment was induced primarily through autophagy and ER stress. In an orthotopic breast cancer mouse model, the combination treatment showed a greater inhibition of tumor growth. In addition, SAHA inhibited the migration and invasion abilities of 4T1 cells and inhibited breast cancer cell migration by inhibiting the activity of MMP-9. In an in vivo experimental metastasis mouse model, SAHA significantly inhibited lung metastasis. SAHA not only enhances radiosensitivity but also suppresses lung metastasis in breast cancer. These novel findings suggest that SAHA alone or combined with IR could serve as a potential therapeutic strategy for breast cancer.

Original languageEnglish
Article numbere76340
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 10 2013

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hydroxamic acids
histone deacetylase
Histone Deacetylase Inhibitors
Radiation Tolerance
metastasis
breast neoplasms
Ionizing radiation
lungs
Cells
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Lung
Ionizing Radiation
Estrogen Receptors
Tumors
ionizing radiation
Cell Line
DNA
Progesterone Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Enhances Radiosensitivity and Suppresses Lung Metastasis in Breast Cancer In Vitro and In Vivo. / Chiu, Hui Wen; Yeh, Ya Ling; Wang, Yi Ching; Huang, Wei Jan; Chen, Yi An; Chiou, Yi Shiou; Ho, Sheng Yow; Lin, Pinpin; Wang, Ying Jan.

In: PLoS One, Vol. 8, No. 10, e76340, 10.10.2013.

Research output: Contribution to journalArticle

Chiu, Hui Wen ; Yeh, Ya Ling ; Wang, Yi Ching ; Huang, Wei Jan ; Chen, Yi An ; Chiou, Yi Shiou ; Ho, Sheng Yow ; Lin, Pinpin ; Wang, Ying Jan. / Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Enhances Radiosensitivity and Suppresses Lung Metastasis in Breast Cancer In Vitro and In Vivo. In: PLoS One. 2013 ; Vol. 8, No. 10.
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