Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective

Balakin, Konstantin V.; Ivanenkov, Yan A.; Kiselyov, Alex S.; Ткаченко, С. Е.

doi:10.2174/187152007781668698

Cited by 32 publications

(25 citation statements)

References 98 publications

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“…Inhibition of HDAC activity exhibits immunosuppressive and anti-inflammatory properties by reducing cytokine production in both humans and mice (6,22,30,59). HDAC inhibition also reduces disease severity in several animal models of inflammatory and autoimmune diseases (6,43,48).…”

Section: Discussionmentioning

confidence: 99%

“…HDAC inhibition also reduces disease severity in several animal models of inflammatory and autoimmune diseases (6,43,48). In endothelial cells, HDAC inhibitors have been shown to suppress thrombin-induced EBD (49).…”

Section: Discussionmentioning

confidence: 99%

“…HDAC6 acetylation results in nuclear translocation and regulation of gene expression (38). HDAC inhibitors exhibit anti-inflammatory properties by suppressing proinflammatory cytokine production (6,22,30,59) and reducing disease severity in animal models of inflammatory and autoimmune disease (6,43,48). In endothelial cells, HDAC inhibitors suppress thrombin-induced EBD (49).…”

Section: Lps Potentiates Hsp90 Chaperone Function By Inducing Pp60mentioning

confidence: 99%

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Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function

Joshi

Barabutis

Birmpas

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 chaperone function, and attenuated RhoA activity and signaling crucial to endothelial barrier function. Treatment with the HDAC3-selective inhibitor RGFP-966 or the HDAC6-selective inhibitor tubastatin A provided partial protection against LPS-mediated transendothelial hyperpermeability. Similarly, knock down of HDAC3 and HDAC6 by specific small-interfering RNAs provided significant protection against LPS-induced EBD. Furthermore, combined pharmacological inhibition of both HDAC3 and -6 attenuated the inflammation, capillary permeability, and structural abnormalities associated with LPS-induced ALI in mice. Together these data indicate that HDAC mediate increased transendothelial hyperpermeability caused by LPS and that inhibition of HDAC protects against LPS-mediated EBD and ALI by suppressing Hsp90-dependent RhoA activity and signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lps Potentiates Hsp90 Chaperone Function By Inducing Pp60mentioning

confidence: 99%

See 1 more Smart Citation

Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function

Joshi

Barabutis

Birmpas

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…So far, at least 80 clinical trials are under way to test >11 different HDAC inhibitory agents targeted toward class I and II HDACs against both hematological and solid malignancies (Tan et al 2010). The clinical activity of HDACis is thought to be due to the more open chromatin structure and potential reactivation of aberrantly suppressed genes, leading to growth arrest, cell differentiation, and apoptosis of tumor cells (Vigushin and Coombes 2002;Balakin et al 2007;Mottet and Castronovo 2008;Shankar and Srivastava 2008;Witt et al 2009;Tan et al 2010). These inhibitors also influence the DNA damage response through acetylation of key DNA repair and checkpoint proteins (Choudhary et al 2009;Robert et al 2011).…”

mentioning

confidence: 99%

Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2

Zhang¹,

Kan²,

Huang³

et al. 2011

Genes Dev.

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Histone deacetylases (HDACs) are major epigenetic modulators involved in a broad spectrum of human diseases including cancers. Administration of HDAC inhibitors (HDACis) leads to growth inhibition, differentiation, and apoptosis of cancer cells. Understanding the regulatory mechanism of HDACs is imperative to harness the therapeutic potentials of HDACis. Here we show that HDACi-and DNA damage-induced apoptosis are severely compromised in mouse embryonic fibroblasts lacking a HECT domain ubiquitin ligase, Mule (Mcl-1 ubiquitin ligase E3). Mule specifically targets HDAC2 for ubiquitination and degradation. Accumulation of HDAC2 in Mule-deficient cells leads to compromised p53 acetylation as well as crippled p53 transcriptional activation, accumulation, and apoptotic response upon DNA damage and Nutlin-3 treatments. These defects in Mule-null cells can be partially reversed by HDACis and fully rescued by lowering the elevated HDAC2 in Mule-null cells to the normal levels as in wild-type cells. Taken together, our results reveal a critical regulatory mechanism of HDAC2 by Mule and suggest this pathway determines the cellular response to HDACis and DNA damage.

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“…induce acetylation of histones, modify the expression of oncogenes and tumor suppressor genes, rescue normal cell growth and differentiation, and thus elicit anticancer effect (Balakin et al, 2007). Sodium valproate is a traditional anti-epilepsy drug with few side effects and excellent tolerability for long-term use.…”

Section: 6429 Effects Of Sodium Valproate On the Growth Of Human Ovamentioning

confidence: 99%

Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910

Yan

Zhang²

2012

Asian Pacific Journal of Cancer Prevention

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To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and G 0 / G 1 phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer. Keywords: Ovarian cancer -apoptosis -WWOX -P27 -sodium valproate RESEARCH ARTICLE Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910Hong-Chao Yan*, Jie Zhang an experimental cell model and the effects of sodium valproate has been investigated on its proliferation, cell cycle, and apoptosis. Materials and Methods Cell CultureHO8910 ovarian cancer cell line, obtained from the Gynecology Department Laboratory of our hospital, Xuzhou, China, were cultured in RPMI 1640 (Hangzhou Sijiqing Biology Engineering Materials Co., Ltd. China) medium supplemented with 10% fetal bovine serum (Hangzhou Sijiqing Biology Engineering Materials Co., Ltd. China), penicillin and streptomycin, in a humidified atmosphere containing 5% CO 2 at 37°C. Experimental groupingThe HO8910 cells were randomly divided into a control group and experiment groups. The experiment groups were cultured in the medium with 1.0, 2.0, 3.0 and 4.0 mmol/L concentrations of sodium valproate (Sigma aldrich, USA), while normal culture medium had been used in the control group. Methylthiazol tetrazolium (MTT) Cell Proliferation AssayMTT cell proliferation assay kit (Beyotime, China) was used for this assay. Briefly, HO8910 cells were trypsinized

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Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective

Cited by 32 publications

References 98 publications

Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function

Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function

Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2

Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910

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