A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer

doi:10.3390/cancers11111703

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Title:	A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer
Authors:	Chiu, Hui-Wen Yeh, Ya-Ling Ho, Sheng-Yow Wu, Yuan-Hua Bour-Jr Wang(王伯智) Huang, Wei-Jan Ho, Yuan-Soon Wang, Ying-Jan Chen, Li-Ching Tu, Shih-Hsin
Contributors:	Taipei Med Univ, Coll Med, Grad Inst Clin Med Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Nephrol Natl Cheng Kung Univ, Coll Med, Dept Environm & Occupat Hlth Chi Mei Med Ctr, Dept Radiat Oncol Chang Jung Christian Univ, Grad Inst Med Sci Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Radiat Oncol Natl Cheng Kung Univ Hosp, Dept Occupat & Environm Med Chia Nan Univ Pharm & Sci, Inst Cosmet Sci Taipei Med Univ, Grad Inst Pharmacognosy Taipei Med Univ, TMU Res Ctr Canc Translat Med Taipei Med Univ, Coll Med, Grad Inst Med Sci Taipei Med Univ Hosp, Dept Lab Med Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol Taipei Med Univ Hosp, Dept Surg, Div Breast Surg Taipei Med Univ, Taipei Canc Ctr Taipei Med Univ, Coll Med, Sch Med, Dept Surg
Keywords:	histone deacetylase inhibitor aggresome radiation autophagy triple-negative breast cancer
Date:	2019
Issue Date:	2020-07-29 13:51:29 (UTC+8)
Publisher:	MDPI
Abstract:	Radiation therapy (RT) is one of the main treatments for triple-negative breast cancer (TNBC). However, many patients experience RT failure due to the metastatic potential of RT and the radiation resistance of several cancers. Histone deacetylase inhibitors (HDACis) can serve as radiosensitizers. In this study, we investigated whether a novel HDACi, TMU-35435, could reinforce radiosensitivity through the induction of misfolded protein aggregation and autophagy in TNBC. Significantly enhanced toxicity was found for the combination treatment compared with TMU-35435 or irradiation (IR) treatment alone in TNBC cells. The combination treatment induced misfolded protein aggregation and TMU-35435 inhibited the interaction of HDAC6 with dynein. Furthermore, the combined treatment induced endoplasmic reticulum (ER) stress but did not trigger apoptosis. In addition, the combination treatment caused autophagic cell death. Tumor growth in the mouse of model orthotopic breast cancer was suppressed by the combination treatment through the induction of ER stress and autophagy. These findings support the future evaluation of the novel HDACi TMU-35435, as a potent radiosensitizer in TNBC.
Relation:	Cancers, v.11, n.11, 1703
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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