Induction of Apoptosis and Autophagy in Breast Cancer Cells by a Novel HDAC8 Inhibitor

Chang Fang Chiu, Hsien Kuo Chin, Wei Jan Huang, Li Yuan Bai, Hao Yu Huang, Jing Ru Weng

Research output: Contribution to journalArticle

Abstract

: Epigenetic therapy has been demonstrated to be a viable strategy for breast cancer treatment. In this study, we report the anti-tumor activity of a hydroxamate-based histone deacetylase (HDAC)8-selective inhibitor, HMC, in breast cancer cells. MTT assays showed that HMC inhibited cell viability of MCF-7 and MDA-MB-231 cells with IC50 values of 7.7 μM and 9.5 μM, respectively. HMC induced caspase-dependent apoptosis in MCF-7 cells, which was associated with its ability to modulate a series of cell survival-related signaling effectors, including Akt, mTOR, Bax, Mcl-1, and Bcl-2. Additionally, HMC was capable of activating PPARγ, which was accompanied by reduced expression of PPARγ target gene products, such as cyclin D1 and CDK6. HMC increased the production of ROS in MCF-7 cells, which could be partially reversed by the cotreatment with a ROS scavenger (N-acetylcysteine or glutathione). Furthermore, HMC induced autophagy, as characterized by the formation of acidic vesicular organelles and autophagic biomarkers including LC3B-II and Atg5. Notably, pharmacological blockade of autophagy by 3-MA or CQ could attenuate HMC-induced apoptosis, suggesting that autophagy played a self-protective role in HMC-induced cell death. Together, these data suggest the translational potential of HMC to be developed into a potential therapeutic agent for breast cancer therapy.

Original languageEnglish
JournalBiomolecules
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 4 2019

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Autophagy
Peroxisome Proliferator-Activated Receptors
MCF-7 Cells
Cells
Apoptosis
Breast Neoplasms
Cell Survival
Histone Deacetylases
Oncology
Cyclin D1
Acetylcysteine
Biomarkers
Cell death
Caspases
Epigenomics
Organelles
Inhibitory Concentration 50
Glutathione
Tumors
Assays

Keywords

  • apoptosis
  • autophagy
  • breast cancer
  • HDAC8-selective inhibitor
  • histone deacetylase
  • PPARγ
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Induction of Apoptosis and Autophagy in Breast Cancer Cells by a Novel HDAC8 Inhibitor. / Chiu, Chang Fang; Chin, Hsien Kuo; Huang, Wei Jan; Bai, Li Yuan; Huang, Hao Yu; Weng, Jing Ru.

In: Biomolecules, Vol. 9, No. 12, 04.12.2019.

Research output: Contribution to journalArticle

Chiu, Chang Fang ; Chin, Hsien Kuo ; Huang, Wei Jan ; Bai, Li Yuan ; Huang, Hao Yu ; Weng, Jing Ru. / Induction of Apoptosis and Autophagy in Breast Cancer Cells by a Novel HDAC8 Inhibitor. In: Biomolecules. 2019 ; Vol. 9, No. 12.
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