Psammaplin A is a natural prodrug that inhibits class I histone deacetylase

Hoon Kim Dong, Jongheon Shin, Jeong Kwon Ho

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Histone deacetylase (HDAC) has been highlighted as one of key players in tumorigenesis and angiogenesis. Recently, several derivatives of psammaplin (Psams) from a marine sponge have been known to inhibit the HDAC activity, but the molecular mechanism for the inhibition has not fully understood. Here, we explored the mode of action of Psams for the inhibition of HDAC activity in the molecular and cellular level. Among the derivatives, psammaplin A (Psam A) showed the potent inhibitory activity in enzyme assay and anti-proliferation assay with IC50 value of 0.003 and 1 μM, respectively. Psam A selectively induced hyperacetylation of histones in the cells, resulting in the upregulation of gelsolin, a well-known HDAC target gene, in a transcriptional level. In addition, reduced Psam A showed a stronger inhibitory activity than that of non-reduced one. Notably, glutathione-depleted cells were not sensitive to Psam A, implying that cellular reduction of the compound is responsible for the HDAC inhibition of Psam A after uptake into the cells. Together, these data demonstrate that Psam A could exhibit its activity under the reduced condition in the cells and be a new natural prodrug targeting HDAC.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalExperimental and Molecular Medicine
Volume39
Issue number1
Publication statusPublished - 2007 Feb 28

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Histone Deacetylases
Prodrugs
Assays
Gelsolin
Derivatives
Enzyme Assays
Porifera
Histones
Inhibitory Concentration 50
Glutathione
psammaplin A
Carcinogenesis
Up-Regulation
Genes
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics

Cite this

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Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. / Dong, Hoon Kim; Shin, Jongheon; Ho, Jeong Kwon.

In: Experimental and Molecular Medicine, Vol. 39, No. 1, 28.02.2007, p. 47-55.

Research output: Contribution to journalArticle

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