Abstract

Accumulation of genetic and epigenetic changes contributes to cancer development and progression. Compared with gene mutations or deletions, epigenetic changes are reversible, which alter the chromatin structure remodeling instead of changes in DNA sequence, and therefore become a promising strategy for chemotherapy. Histone deacetylases (HDACs) are a class of enzymes that responsible for the epigenetic regulation of gene expression. MPT0G030 is a potent and selective class I HDAC inhibitor which showed broad-spectrum cytotoxicity against various human cancer cell lines. in vitro fluorometric HDAC activity assay showed that MPT0G030 effectively inhibited Class I HDACs (HDAC1~3), which were overexpressed in many malignant neoplasms. Interestingly, MPT0G030 not only induced histone acetylation and tumor suppressor p21 transcription, but also redistributed E-cadherin and activated Protein Kinase C δ (PKCδ), which was linked to cell apoptosis and differentiation. Further, activation of PKCδ was demonstrated to be modulated through HDAC1. The in vivo anticancer activity of MPT0G030 and the importance of PKCδ were confirmed in the HT-29 tumor xenograft models. Taken together, those results indicate that MPT0G030, a class I HDAC inhibitor, has great potential as a new drug candidate for cancer therapy.

Original languageEnglish
Pages (from-to)5651-5662
Number of pages12
JournalOncotarget
Volume5
Issue number14
Publication statusPublished - 2014

Fingerprint

Histone Deacetylases
Cadherins
Protein Kinase C
Cell Differentiation
Colorectal Neoplasms
Apoptosis
Epigenomics
Neoplasms
Chromatin Assembly and Disassembly
Sequence Deletion
Gene Expression Regulation
Acetylation
Heterografts
Histones
Drug Therapy
Cell Line
Enzymes
Pharmaceutical Preparations
Genes

Keywords

  • Differentiation
  • E-cadherin
  • HDAC
  • MPT0G030
  • PKCδ

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

A novel class I HDAC inhibitor, MPT0G030, induces cell apoptosis and differentiation in human colorectal cancer cells via HDAC1/PKCδ and E-cadherin. / Wang, Li Ting; Liou, Jing Ping; Li, Yu Hsuan; Liu, Yi Min; Pan, Shiow Lin; Teng, Che Ming.

In: Oncotarget, Vol. 5, No. 14, 2014, p. 5651-5662.

Research output: Contribution to journalArticle

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