Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion

Yee, Su-Bog; Kim, Myoung Soo; Baek, Soo Jin; Kim, Gyoo Cheon; Yoo, Kisoo; Yoo, Young Hyun; Park, Bong Soo

doi:10.3892/ijo.25.5.1431

Cited by 9 publications

(10 citation statements)

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“…In our experiments, the concentration of TSA was almost the same or even higher (up to 1 M) than the concentration that induces apoptosis in cancer cells (17,18,(35)(36)(37), but we could not find any toxicity in human RPTEC. Recently, it was reported that HDAC inhibitors induced tumor-selective toxicity through activation of the death receptor pathway (38).…”

Section: Discussionmentioning

confidence: 52%

Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Renal Epithelial Cells

Yoshikawa¹,

Hishikawa²,

Marumo³

et al. 2007

Journal of the American Society of Nephrology

192

174

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Section: Discussionmentioning

confidence: 52%

Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Renal Epithelial Cells

Yoshikawa¹,

Hishikawa²,

Marumo³

et al. 2007

Journal of the American Society of Nephrology

192

174

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“…Although TSA is reported to inhibit cell growth and induce apoptosis of various cancer cells (Roh et al, 2004;Yee et al, 2004), there is little evidence of its pharmacologic efficacy on lung cancer cells. Choi demonstrated that TSA induces apoptotic death of A549 lung cancer cell (Choi, 2005).…”

Section: Discussionmentioning

confidence: 99%

Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway

Kim

Kim²,

Yang³

et al. 2006

Exp Mol Med

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Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deacetylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of transformed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung cancer cells is not clearly known yet. Herein, we demonstrated that treatment of TSA resulted in a significant decrease of the viability of H157 cells in a dose-dependent manner, which was revealed as apoptosis accompanying with nuclear fragmentation and an increase in sub-G 0 /G 1 fraction. In addition, it induced the expression of Fas/FasL, which further triggered the activation of caspase-8. Catalytic activation of caspase-9 and decreased expression of anti-aptototic Bcl-2 and Bcl-XL proteins were observed in TSA-treated cells. Catalytic activation of caspase-3 by TSA was further confirmed by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction, including mitochondrial membrane potential transition and release of mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells. Taken together, our data indicate that inhibition of HDAC by TSA induces the apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic and mitocondria-mediated intrinsic caspases pathway.

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“…22 Another HDACi, trichostatin A, was shown to induce apoptosis in the P815 cell line via histone-dependent and intrinsic apoptosis pathways. 31 The purpose of this study was to further characterize the biologic effects of HDAC inhibition with AR-42 on malignant mast cells and demonstrate that AR-42 induces down-regulation of Kit expression in all cell lines through both transcriptional down-regulation and loss of chaperone (HSP90) activity.Hyperacetylation of histones H3 and H4 is an important biomarker for HDAC inhibition, as this is necessary for restoration of gene expression. Although hyperacetylation of H3 and H4 occurred in all cell lines and tumor samples tested after AR-42 treatment, up-regulation of the cyclin-dependent kinase inhibitor p21 was observed only in the C2 line, canine BMCMCs, and MCT patient no.…”

mentioning

confidence: 99%

AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit

Lin¹,

Fenger²,

Murahari³

et al. 2010

Blood

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Histone hypoacetylation occurs in many cancers and inhibition of histone deacetylation is a promising approach to modulate these epigenetic changes. Our laboratory previously demonstrated that the histone deacetylase inhibitors (HDACis) vorinostat and AR-42 reduced the viability of a canine malignant mast cell line. The purpose of this study was to further investigate the mechanisms of pan-HDAC inhibition in normal and malignant mast cells. Mouse and canine malignant mast cell lines expressing various Kit mutations, normal canine mast cells, and primary canine malignant mast cells were treated with AR-42 (a novel HDACi) and effects on cell viability, cycling, and signaling were evaluated. Treatment with AR-42 induced growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7. AR-42 promoted hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. Down-regulation of Kit occurred after AR-42 treatment via inhibition of Kit transcription. Disassociation between Kit and heat shock protein 90 (HSP90) and up-regulation of HSP70 were observed after AR-42 treatment, suggesting potential loss of HSP90 chaperone function. Lastly, AR-42 down-regulated the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. In summary, AR-42 exhibits in vitro and ex vivo biologic activity against malignant mast cells, representing a promising therapeutic approach for malignant mast cell disease.

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Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion

Cited by 9 publications

References 0 publications

Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Renal Epithelial Cells

Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Renal Epithelial Cells

Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway

AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit

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