Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing

Ahn, Mee Young; Kang, Dong Oh; Na, Yong Jin; Yoon, Sungpil; Choi, Whan Soo; Kang, Keun Wook; Chung, Hae Young; Jung, Jee H.; Min, Do Sik; Kim, Hyung Sik

doi:10.1016/j.canlet.2012.06.017

Cited by 46 publications

(57 citation statements)

References 53 publications

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“…HDAC inhibitors have been represented as a new generation of anti-cancer agents, as one class of them, a variety of natural cyclic peptide HDAC inhibitors and synthetic analogues have been found and explored their HDAC isoform-selectivity Walton, 2006;Bhuiyan et al, 2006;Gu et al, 2007;Matsuoka et al, 2007;Wang et al, 2007;Im et al, 2008;Norikazu et al, 2008;Ahn et al, 2012) owing to their stable conformation and considerable efficacy. Here, we reported several studies about synthetic bicyclic tetrapeptide compounds containing hydroxamic-acid involving binding mode with HDAC4, anti-proliferation cell cycle arrest and apoptosis inducement with three hematological cancer cell lines K562, HL60 and U937 as objects.…”

Section: Discussionmentioning

confidence: 99%

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell

Li¹,

Huang²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Histone deacetylase (HDAC) inhibitors of cyclic peptide have been proved to be the most complex but the most stable and relative efficient inhibitors because of their large cap region. In this paper, a series of studies were carried out to evaluate the efficacy of synthetic bicyclic tetrapeptide inhibitors 1-5 containing hydroxamic acid referring molecular docking, anti-proliferation, morphology and apoptosis. Docking analysis, together with enzyme inhibitory results, verified the selective capability of inhibitor 4 to HDAC4, which might closely related to haematological tumorigenesis, with Phe227, Asp115, Pro32, His198 and Ser114 participating into hydrophobic interactions and Van der Waals force which was familiar with former study. Moreover, inhibitor 4 inhibited K562 cell line at the IC 50 value of 1.22 µM which was 51-67 times more efficient than that for U937 and HL60 cell lines. Inhibitor 4 exhibited the cell cycle-arrested capability to leukemia at S phase or G2/M phase as well as apoptosis-induced ability in different degrees. Finally, we considered that bicyclic tetrapeptide inhibitors were promising inhibitors used in cancer treatment and inhibitor 4 could prevent K562 cell line well from proliferation, arrest cell cycle and induce K562 towards apoptosis to achieve the goals of reversing cancer cells which could become a potential leukemia therapeutic agent in the future.

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Section: Discussionmentioning

confidence: 99%

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell

Li¹,

Huang²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Notably, several previous studies reported that up-regulation of RECK resulted in decreased ovarian cancer amplification [14]. In addition, histone deacetylase inhibitor inhibited ovarian cancer cell migration partially through up-regulation of RECK [15]. …”

Section: Introductionmentioning

confidence: 99%

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Shen¹,

Bang-hua²,

Zhang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.

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“…It has been shown to exhibit antitumor effects in several human cancer cell lines, including leukemia (Kwon et al, 2002), ovarian (Ahn et al, 2012), endometrial (Ahn et al, 2010), oral squamous (Ahn et al, 2011), cervical (Han et al, 2000;Luczak and Jagodzinski, 2008), and breast (Han et al, 2000) cancer cell lines in vitro and in vivo (Lai et al, 2009). The therapeutic potential of apicidin also appears promising in combination therapy with other agents such as docetaxel (Buoncervello et al, 2012), doxorubicin (Lai et al, 2009), and tumor necrosis factor-related apoptosis-inducing ligand (Park et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

et al. 2014

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Apicidin, a potential oral chemotherapeutic agent, possesses potent anti-histone-deacetylase activity. After oral administration, the total bioavailability of apicidin is known to be low (14.2%-19.3%). In the present study, we evaluated the factors contributing to the low bioavailability of apicidin by means of quantitative determination of absorption fraction and first-pass metabolism after oral administration. Apicidin was given to rats by five different routes: into the femoral vein, duodenum, superior mesenteric artery, portal vein, and carotid artery. Especially, the fraction absorbed (F X ) and the fraction that is not metabolized in the gut wall (F G ) were separated by injection of apicidin via superior mesenteric artery, which enables bypassing the permeability barrier. The F X was 45.9% 6 9.7%, the F G was 70.9% 6 8.1% and the hepatic bioavailability (F H ) was 70.6% 6 12.3%, while the pulmonary firstpass metabolism was minimal (F L = 102.8% 6 7.4%), indicating that intestinal absorption was the rate-determining step for oral absorption of apicidin. The low F X was further examined in terms of passive diffusion and transporter-mediated efflux by in vitro immobilized artificial membrane (IAM) chromatographic assay and in situ single-pass perfusion method, respectively. Although the passive diffusion potential of apicidin was high (98.01%) by the IAM assay, the in situ permeability was significantly enhanced by the presence of the P-glycoprotein (P-gp) inhibitor elacrider. These data suggest that the low bioavailability of apicidin was mainly attributed to the P-gp efflux consistent with the limited F X measured in vivo experiment.

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Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing

Cited by 46 publications

References 53 publications

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

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