Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines

Yutaka Hoshikawa, Ho Jeong Kwon, Minoru Yoshida, Sueharu Horinouchi, Teruhiko Beppu

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Trichostatin A (TSA) is a Streptomyces metabolite which specifically inhibits mammalian histone deacetylase at a nanomolar concentration and causes accumulation of highly acetylated histone molecules in mammalian cells. The effects of TSA on the morphology and the cell cycle of the human carcinoma cell lines, T24 and HeLa, were investigated. The morphology of T24 and HeLa cells dramatically changed and actin stress fibers reappeared during the treatment with TSA. The morphological change was not observed with chemically synthesized (S)-TSA and trichostatic acids, which are inactive to inhibit histone deacetylase. Cell cycle progression of these cells was blocked by TSA at G1 phase (HeLa) or G1 and G2 phases (T24). An RNA synthesis inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide, inhibited the morphological changes by TSA, suggesting that TSA induces expression of a new gene(s) followed by de novo protein synthesis, which is required for the actin microfilament reorganization. An approximately 7-fold (T24) or 12-fold (HeLa) increase in the intracellular level of gelsolin, an actin regulatory protein, was found in the cells treated with TSA for 24 h. These results suggest that gelsolin is one of the putative proteins necessary for the morphological changes of human carcinoma cells induced by TSA.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalExperimental Cell Research
Volume214
Issue number1
DOIs
Publication statusPublished - 1994 Jan 1

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trichostatin A
Gelsolin
Histone Deacetylases
Carcinoma
Cell Line
G1 Phase
Actins
Cell Cycle
Nucleic Acid Synthesis Inhibitors
Stress Fibers
Proteins
Protein Synthesis Inhibitors
G2 Phase
Streptomyces
Dactinomycin
Cycloheximide
Actin Cytoskeleton
HeLa Cells
Histones

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Hoshikawa, Yutaka ; Kwon, Ho Jeong ; Yoshida, Minoru ; Horinouchi, Sueharu ; Beppu, Teruhiko. / Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines. In: Experimental Cell Research. 1994 ; Vol. 214, No. 1. pp. 189-197.
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Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines. / Hoshikawa, Yutaka; Kwon, Ho Jeong; Yoshida, Minoru; Horinouchi, Sueharu; Beppu, Teruhiko.

In: Experimental Cell Research, Vol. 214, No. 1, 01.01.1994, p. 189-197.

Research output: Contribution to journalArticle

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