Apicidin is a histone deacetylase inhibitor with anti-invasive and anti-angiogenic potentials

doi:10.1016/j.bbrc.2004.01.149

Biochemical and Biophysical Research Communications

Volume 315, Issue 4, 19 March 2004, Pages 964-970

https://doi.org/10.1016/j.bbrc.2004.01.149 Get rights and content

Abstract

Apicidin has been identified as a histone deacetylase (HDAC) inhibitor. Since HDAC inhibitors are emerging as an exciting new class of potential anti-cancer agents, in the present study, we have examined the inhibitory effect of apicidin on cancer invasion and angiogenesis. Apicidin induced di- and tri-acetylated forms of histone H4 and the morphological alteration in v-ras-transformed mouse fibroblast NIH3T3 cells. Apicidin dramatically inhibited the invasion of v-ras-NIH3T3 and human melanoma A2058 cells and it could be associated with its ability to regulate the activities of matrix metalloproteinases. Interestingly, apicidin strongly inhibited the formation of new vessels on chorioallantoic membrane and the tube formation of ECV304 human vascular endothelial cells. This is the first report to show the anti-angiogenic potential of apicidin and it could be developed as a new type of anti-cancer drug.

Section snippets

Materials and methods

Materials. Apicidin, [cyclo(N-O-methyl-l-tryptophanyl-l-isoleucinyl-d-pipecolinyl-l-2-amino-8-oxodecanoyl)], was prepared from Fusarium sp. Strain KCTC 16677 according to the method previously described [14] and resuspended in dimethyl sulfoxide (DMSO). All other chemicals were of the highest quality commercially available.

Cells and cell culture. The v-ras-transformed mouse fibroblast NIH3T3 cells, human melanoma A2058 cells, and human breast cancer cells (MDA-MB-435s and MCF-7) were cultured

Results

In the previous study, to examine the effect of apicidin on the proliferation of mouse and human cancer cell lines, cell growth inhibition was assessed with the SRB protein dye assay 48 h after cell seeding at 1 × 10⁵ cells/well in 6-well plates in complete growth medium [12]. In this assay, cell growth was inhibited to various degrees in the presence of apicidin, having half-maximum effects between 1.8 and 0.1 g/ml (IC₅₀=0.18, 0.55, and 1.17 μg/ml in v-ras-NIH3T3, A2058, and MCF7, respectively).

Discussion

Since tumor metastasis is the process that requires for malignant cells to leave the primary tumor and proliferate at a distant site, this process is the leading cause of death in cancer patients. Tumor metastasis is characterized with several steps: invasion (matrix degradation and cell motility), intravasation, cell attachment, extravasation, cell proliferation, and vessel formation (angiogenesis) [17]. Recently, HDAC inhibitors are emerging as an exciting new class of potential anti-cancer

Acknowledgements

This work was supported by research Grant No. KPRC-99-KA-1-3 from Kyonggi Pharmaceutical Research Center.

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¹: These authors contributed equally to this work and are equal first authors.

View full text

Apicidin is a histone deacetylase inhibitor with anti-invasive and anti-angiogenic potentials

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

On the biological role of histone acetylation

Biochem. J.

Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase

J. Biol. Chem.

A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors

Proc. Natl. Acad. Sci. USA

Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A

J. Biol. Chem.

Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase

Proc. Natl. Acad. Sci. USA

Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion

Cancer Res.

Trichostatin A, an inhibitor of histone deacetylase, inhibits hypoxia-induced angiogenesis

Expert Opin. Invest. Drugs

Depudecin, a microbial metabolite containing two epoxide groups, exhibits anti-angiogenic activity in vivo

Biol. Pharm. Bull.

Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells

J. Biol. Chem.

Histone deacetylase inhibitors in cancer treatment

Anticancer Drugs

Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase

Proc. Natl. Acad. Sci. USA

Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin

Cancer Res.

Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype

Cancer Lett.

A hemorrhagic factor (Apicidin) produced by toxic Fusarium isolates from soybean seeds

Appl. Environ. Microbiol.