Disease relevance of apicidin

• Similarly, apicidin notably induced the apoptosis in the primary leukemic blasts obtained from chronic myelogenous leukemia patients in blast crisis [1].
• One of these, a culture of Fusarium sp. strain KCTC 16677, produced apicidin, an antiprotozoal agent that caused toxic effects in rats (including body weight loss; hemorrhage in the stomach, intestines, and bladder; and finally death) when rats were fed diets supplemented with 0.05 and 0.1% apicidin [2].
• 1 We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n-butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into eosinophils [3].
• 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 [4].
• The findings raise the possibility that apicidin may prove particularly effective in the treatment of endometrial and ovarian cancers [5].

High impact information on apicidin

• (3) SULF1 enhanced the induction of apoptosis by the HDAC inhibitors apicidin and scriptaid [6].
• Induction of fetal hemoglobin expression by the histone deacetylase inhibitor apicidin [7].
• Additionally, activation of the Agamma-globin promoter by apicidin could be inhibited by p38 inhibitor SB203580 [7].
• Activation of NF-kappaB by HDAC inhibitor apicidin through Sp1-dependent de novo protein synthesis: its implication for resistance to apoptosis [8].
• This NF-kappaB activation contributes to resistance of HeLa cells to apoptotic potential of apicidin [8].

Biological context of apicidin

• We also demonstrate that knockdown of SULF1 with shRNA constructs up-regulates phosphorylation of AKT and Erk and attenuates apicidin-induced apoptosis [6].
• Taken together, the results suggest that induction of histone hyperacetylation by apicidin is responsible for the antiproliferative activity through selective induction of genes that play important roles in the cell cycle and cell morphology [9].
• In parallel, apicidin treatment leads to histone hyperacetylation in the IL-8 promoter region independent of NF-kappaB signaling pathway, which is not sufficient for full transcription of IL-8 gene [8].
• The antiproliferative activity of apicidin on HeLa cells was accompanied by morphological changes, cell cycle arrest at G1 phase, and accumulation of hyperacetylated histone H4 in vivo as well as inhibition of partially purified HDAC in vitro [9].
• We previously reported that apicidin arrested human cancer cell growth through selective induction of p21(WAF1/Cip1) [10].

Anatomical context of apicidin

• In summary, the novel HDAC inhibitor apicidin was found to be a potent inducer of HbF synthesis in K562 cells [7].
• Apicidin showed a broad spectrum of antiproliferative activity against various cancer cell lines, although with differential sensitivity [9].
• In this study, the apoptotic potential of apicidin and its mechanism in HL60 cells was investigated [10].
• Taken together, the results suggest that apicidin might induce apoptosis through selective induction of Fas/Fas ligand, resulting in the release of cytochrome c from the mitochondria to the cytosol and subsequent activation of caspase-9 and caspase-3 [10].
• Interestingly, apicidin strongly inhibited the formation of new vessels on chorioallantoic membrane and the tube formation of ECV304 human vascular endothelial cells [4].

Associations of apicidin with other chemical compounds

• In contrast to other HDAC inhibitors such as apicidin, the extrinsic, receptor-mediated pathway played a minimal role in MS-275 lethality [11].
• The addition of cycloheximide greatly inhibited activation of caspase-3 by apicidin by interfering with cleavage of procaspase-3 and DNA fragmentation, suggesting that apicidin-induced apoptosis was dependent on de novo protein synthesis [10].
• 3 Apicidin (100 nm) as well as n-butyrate (500 microm) induced continuous acetylations of histone H4 and lysine14 residue on histone H3, while TSA (30 nm) induced transient acetylations [3].
• Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product [12].
• We investigated the induction of the human fetal globin gene using five potent histone deacetylase (HDAC) inhibitors: FK-228, HC-Toxin, Trichostatin, MS-275, and Apicidin, using in vitro assays and cultures of primary human erythroblasts [13].
• The combination of doxorubicin with apicidin significantly increased the anti-tumor effect in the SULF1-expressing Huh7 and Hep3B cells as compared to either apicidin or doxorubicin alone, both in vitro and in vivo [14].

Gene context of apicidin

• In addition, apicidin induced selective changes in the expression of p21WAF1/Cip1 and gelsolin, which control the cell cycle and cell morphology, respectively [9].
• In addition, our data show that the early expression of TNF-alpha does not lead to activation of NF-kappaB, because disruption of TNF-alpha activity by a neutralizing antibody does not affect nuclear translocation of NF-kappaB, IkappaBalpha degradation or reporter gene activation by apicidin [15].
• Furthermore, apicidin activation of NF-kappaB seems to result from HDAC1 inhibition, as evidenced by the observation that overexpression of HDAC1, but not HDAC2, 3 or 4, dramatically inhibits NF-kappaB reporter gene activity [15].
• Furthermore, apicidin treatment of these cell lines increased acetylation of H3 and H4 histone tails [5].
• In K562 cells, apicidin at 10-100 nM did not inhibit cell growth nor express CD11b, CD14 and CD15 [16].

Analytical, diagnostic and therapeutic context of apicidin

• The interaction between SULF1 and apicidin was confirmed in vivo in Huh7 and Hep3B xenografts [6].
• The developed assay method was applied to a pharmacokinetic study after intravenous injection of apicidin in rats at a dose of 1 mg/kg [17].
• To our knowledge, this study is the first to describe a rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method for the quantification of apicidin in rat serum [17].
• Chromatin immunoprecipitation shows p21 promoter DNA is associated with hyperacetylated histones H3 and H4 after treatment with apicidin [18].
• This study is the first report of the pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats after i.v. and oral administration [19].

References