Inhibition of bladder tumour growth by histone deacetylase inhibitor

Ozawa, A.; Tanji, Nozomu; Kikugawa, Tadahiko; Sasaki, Toyokazu; Yanagihara, Yoshio; Miura, Noriyoshi; Yokoyama, Masayoshi

doi:10.1111/j.1464-410x.2009.08795.x

Cited by 40 publications

(33 citation statements)

References 20 publications

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“…Valproic acid not only suppressed some tumor growth and metastasis, but also induced tumor differentiation in vitro and in vivo (Blaheta and Cinatl 2002). Valproic acid inhibited the in vitro and in vivo cancer cell growth of melanoma (Landreville et al 2012), urinary bladder cancer (Byun et al 2009;Ozawa et al 2010), breast cancer (Munster et al 2009), and prostate cancer (Chou et al 2011). Recently, the combination of valproic acid with other anticancer agents has been considered as a useful and necessary strategy to inhibit tumor growth and progression (Byun et al 2009;Munster et al 2009;Ozawa et al 2010;Chou et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Enhanced suppression of proliferation and migration in highly-metastatic lung cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and its molecular mechanisms of action

et al. 2012

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Valproic acid (VPA) as a broad-spectrum inhibitor of histone deacetylase, has been used in cancer therapy. Recently, the combination of VPA with other anticancer agents has been considered as a useful and necessary strategy to inhibit tumor growth and progression. The coumarin derivates from natural plants have been shown to be the promising natural anticancer agents. However, no literature is available on the anticancer effects of the combination of VPA and coumarin-3-carboxylic acid (HCCA). Here we show that this combination significantly increases inhibitory effects against the proliferation and migration in highly-metastatic lung cancer cells by inducing apoptosis and cell cycle arrest as well as regulating related protein expressions. Our results indicate that this combination of VPA with HCCA not only enhances the protein levels of Bax, cytosolic cytochrome c, caspase-3 and PARP-1 but also reduces the protein expressions of Bcl-2, cyclin D1 and NF-jB as well as inhibits the phosphorylation and expressions of Akt, EGFR, VEGFR2 and c-Met in the cancer cells. Our results suggest that the combination of VPA with HCCA suppresses the proliferation and migration of lung cancer cells via EGFR/VEGFR2/c-Met-Akt-NFjB signaling pathways; this combination may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of lung cancer.

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Section: Introductionmentioning

confidence: 99%

Enhanced suppression of proliferation and migration in highly-metastatic lung cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and its molecular mechanisms of action

et al. 2012

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“…High expression levels of class I HDACs correlated with tumour dedifferentiation and higher proliferative fractions (measured by Ki-67) in urothelial carcinoma, which is in line with in vitro studies showing that high HDAC activity leads to tumour dedifferentiation and enhanced tumour cell proliferation [28][29][30]. Despite the growth inhibitory effects of HDAC-i demonstrated in various cell lines including bladder cancer cells, a broad expression analysis of this attractive target has not been conducted yet [12][13][14][15][16]31,32].…”

Section: Discussionmentioning

confidence: 62%

“…In contrast to these findings, a more recent study of Xu and colleagues reported no difference of expression in the expression levels of HDAC-2 between normal urothelial and bladder cancer tissue as assessed by immunohistochemistry [13]. Few studies have found an effect for HDAC-inhibitors (HDAC-i) in urothelial cancer cell lines [12,[14][15][16][17], however, a broad expression analysis of HDACs in urothelial carcinomas has not been conducted so far. In addition, there is no study available on the prognostic relevance of class I HDACs in bladder cancer.…”

Section: Introductionmentioning

confidence: 93%

“…Especially, the first three isoforms HDAC-1, −2 and −3 were found to be overexpressed. Contrary to HDAC-8, for which no overexpression was found [2,[9][10][11][12]. In contrast to these findings, a more recent study of Xu and colleagues reported no difference of expression in the expression levels of HDAC-2 between normal urothelial and bladder cancer tissue as assessed by immunohistochemistry [13].…”

Section: Introductionmentioning

confidence: 99%

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920 Expression of Histone Deacetylases 1,2 and 3 in Urothelial Bladder Cancer

Poyet¹,

Jentsch²,

Hermanns³

et al. 2013

Journal of Urology

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Background: Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. In this study we aimed to evaluate the protein expression of class I HDACs in urothelial carcinoma of the bladder. Methods: A tissue microarray containing 348 tissuesamples from 174 patients with a primary urothelial carcinoma of the bladder was immunohistochemically stained for HDAC 1, 2 and 3. Intensity of staining was evaluated and the association with clinico-pathological features and prognosis was assessed. Results: High HDAC expression levels were found in 40 to 60% of all investigated urothelial carcinomas (HDAC-1: 40%, HDAC-2: 42%, HDAC-3: 59%). HDAC-1 and HDAC-2 were significantly associated with higher tumour grades. Although all three markers could not predict progression in univariate analyses, high HDAC-1 expression was associated with a trend toward poorer prognosis. Patients with high-grade tumours and high expression levels of HDAC-1 were more likely to progress compared to all other patients (p < 0.05). Conclusions: High-grade noninvasive papillary bladder tumours are associated with high expression levels of HDAC-1 and HDAC-2. High grade tumours in combination with high expression of HDAC-1 showed a worse prognosis than the other tumours. The high expression levels of HDACs observed particularly in high grade urothelial bladder cancer clearly warrant subsequent studies on the potential use of HDAC inhibitors as a novel therapeutic approach.

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“…Recent studies showed that aberrant expression of HDAC1 was found in various types of cancer cells, which suggested that the HDAC1 expression was associated with tumor progress and differentiation. For example, Ozawa A found that the expression level of HDAC1 mRNA in human urinary bladder cancer specimens was significantly higher than that of normal controls [3]. Also, increased mRNA expressions of HDCA1, HDAC2 and HDAC3 were detected in ovarian cancer tissues, compared to normal tissue samples [4].…”

Section: Introductionmentioning

confidence: 99%

Enhanced radiosensitivity of EC109 cells by inhibition of HDAC1 expression

2010

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Histone deacetylase (HDAC) activity plays the role of deacetylation of histone and non-histone proteins, which can alter gene expression patterns and cell behavior potentially associated with malignant transformation. Aberrant expression of HDAC1 has been found in various types of cancers, which indicated that it might be a target for cancer therapy. In this study, overexpression of HDAC1 was found in esophageal cancer samples by real-time RT-PCR, compared with adjacent non-cancerous tissues. To further verify the possibility of anticancer treatment by silencing the increased HDAC1 in esophageal carcinoma cells, HDAC1 expression was knockdown using plasmid-based RNA interference (RNAi). Results showed the HDAC1 expression was efficiently inhibited and the acetylation of histone H3 was significantly increased by RNAi in EC109 cells. Increased apoptotic cell death was observed when HDAC1 expression was knockdown, which indicated that cells were more sensitive to radiation. Moreover, the results also showed DNA was more easily broken by radiation in EC109 cells when HDAC1 expression was knockdown, as measured by γH2AX foci and single-cell electrophoresis. Our data suggested that targeting the increased HDAC1 expression might be feasible for esophageal cancer therapy.

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Inhibition of bladder tumour growth by histone deacetylase inhibitor

Cited by 40 publications

References 20 publications

Enhanced suppression of proliferation and migration in highly-metastatic lung cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and its molecular mechanisms of action

Enhanced suppression of proliferation and migration in highly-metastatic lung cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and its molecular mechanisms of action

920 Expression of Histone Deacetylases 1,2 and 3 in Urothelial Bladder Cancer

Enhanced radiosensitivity of EC109 cells by inhibition of HDAC1 expression

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