Apicidin, a natural fugal metabolite, is a selective inhibitor of HDAC.
Histone deacetylases (HDAC) are enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. It has been revealed that histone acetyltransferase and histone deacetylase play important roles to either transcriptionally activate or repress gene expression through the reversible acetylation of lysine residues on a histone.
Apicidin has the potent and broad activity against apicomplexan parasites [1]. It has also been shown to have potent anti-angiogenesis activity and decrease HIF-1a levels in both human and mouse cancer cell lines [2].
The component has also been used extensively in vivo study to understand the role of HDAC in different physical processes. Apicidin exhibits anti-proliferative activity against different cancer cells lines in mice [3]. In a human colon HCT-116 carcinoma xenograft model, apicidin suppresses the tumor growth [4]. And it also exhibits the antitumor activity in a Ishikawa cell tumor xenograft model [5].
References:
1.Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, et al. Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci U S A 1996,93:13143-13147.
2.Kim SH, Jeong JW, Park JA, Lee JW, Seo JH, Jung BK, et al. Regulation of the HIF-1alpha stability by histone deacetylases. Oncol Rep 2007,17:647-651.
3.Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res 2000,60:6068-6074.
4.Jones P, Altamura S, De Francesco R, Paz OG, Kinzel O, Mesiti G, et al. A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo. J Med Chem 2008,51:2350-2353.
5.Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS. Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int J Oncol 2010,36:125-131.
