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| 標題: | A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer |
| 作者: | 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 |
| 貢獻者: | 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 |
| 關鍵字: | histone deacetylase inhibitor
aggresome
radiation
autophagy
triple-negative breast cancer |
| 日期: | 2019 |
| 上傳時間: | 2020-07-29 13:51:29 (UTC+8) |
| 出版者: | MDPI |
| 摘要: | 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. |
| 關聯: | Cancers, v.11, n.11, 1703 |
| 顯示於類別: | [化妝品應用與管理系(所)] 期刊論文
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