Inhibition of Histone Deacetylase 10 Induces Thioredoxin-Interacting Protein and Causes Accumulation of Reactive Oxygen Species in SNU-620 Human Gastric Cancer Cells

Lee, Ju Hee; Jeong, Eun Goo; Choi, Myeon-Song; Kim, Sung Hak; Park, Jung Hyun; Song, Sang Hyun; Park, Jinah; Bang, Yung Jue; Kim, Taeyou

doi:10.1007/s10059-010-0094-z

Cited by 69 publications

(55 citation statements)

References 34 publications

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“…Nevertheless, it remains to be clarified how HDAC4 regulates TNFinduced ROS production in SMCs. It is well known that HDACs inhibitors activate genes that promote cell cycle arrest and apoptosis in a number of tumor cells (20). This effect was accompanied by the induction of ROS.…”

Section: Discussionmentioning

confidence: 98%

HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats

Usui

Okada

Mizuno

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Our recent study demonstrated that HDAC4 protein specifically increases in mesenteric artery from spontaneous hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY). Vascular inflammation is important for pathogenesis of hypertension. We examined whether HDAC4 affects vascular inflammatory responses and promotes hypertension. In vivo, blood pressure, reactive oxygen species (ROS) production, and VCAM-1 expression in isolated mesenteric artery were elevated in young SHR (7 wk old) compared with age-matched WKY, which were prevented by long-term treatment of SHR with an HDACs inhibitor, trichostatin A (TSA; 500 g·kg Ϫ1 ·day Ϫ1 for 3 wk). In isolated mesenteric artery, the increased angiotensin II-induced contraction in SHR was reversed by TSA. The endothelium-dependent relaxation induced by ACh in SHR was augmented by TSA. In cultured rat mesenteric arterial smooth muscle cells (SMCs), expression of HDAC4 mRNA and protein was increased by TNF-␣ (10 ng/ml). TSA (10 M, pretreatment for 30 min) inhibited VCAM-1 expression and NF-B phosphorylation induced by TNF (10 ng/ml, 24 h or 20 min) in SMCs. HDAC4 small interfering RNA inhibited TNF-induced monocyte adhesion, VCAM-1 expression, transcriptional activity of NF-B, and ROS production in SMCs. The present results demonstrated that proinflammatory effects of HDACs may mediate the further development of hypertension in SHR. It is also suggested in cultured vascular SMCs that TNF-induced HDAC4 mediates vascular inflammation likely via VCAM-1 induction through ROS-dependent NF-B activation. oxygen radicals; smooth muscle; contractile function CAM IS ASSOCIATED WITH A VARIETY of cell functions including inflammation, apoptosis, and muscular contraction. Recent evidence indicates that CaM-related proteins are responsible for cardiovascular diseases. In the previous study, we compared expression levels of six CaM-related proteins with almost unknown functions in vasculature [CaMKII␦, eukaryotic elongation factor 2 kinase (eEF2K; also known as CaMKIII), histone deacetylase (HDAC)4, HDAC5, death associated protein kinase (DAPK)3, and CaM serine kinase (CASK)] in aorta and mesenteric artery from spontaneous hypertensive rats (SHR) and Wistar Kyoto rats (WKY) (48). As a result, we for the first time demonstrated that expressions of eEF2K, HDAC4, and DAPK3 protein increased in SHR compared with WKY. However, it remained to be clarified how each CaM-related protein might affect vascular pathophysiology and control the development of hypertension.HDACs have been considered as transcriptional corepressors that catalyze histone deacetylation in diverse physiological systems (33, 42). Up to now, HDACs have been classified into four groups termed class I HDACs (HDAC1, 2, 3, and 8), class II HDACs (HDAC4, 5, 6, 7, 9, and 10), class III HDACs, and class IV HDAC (HDAC11). The class II HDACs are further divided into the class IIa (HDAC4, 5, 7, 9) and the class IIb (HDAC6 and 10) (26). A recent study clarified that the class I and IIa HDACs play critical roles in mediating cardiac h...

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Section: Discussionmentioning

confidence: 98%

HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats

Usui

Okada

Mizuno

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…HDAC10 was demonstrated to be a tumor suppresser in some types of cancer, including clear cell renal cell carcinoma (13), cervical cancer (19), gastric cancer (12,20), and ovarian cancer (16). The function of HDAC10 in lung cancer is a matter of debate (10,15).…”

Section: Discussionmentioning

confidence: 99%

“…HDAC10 has been reported to be involved in homologous recombination (3), melanogenesis (4), cells autophagy (5-7), cell cycle regulation (8), DNA mismatch repair (9) and cancer progression (10)(11)(12)(13)(14)(15)(16). While HDAC10 was reported to suppresses the proliferation and invasion of clear cell renal cell carcinoma (13), it was also demonstrated to promote cell proliferation via AKT phosphorylation in lung cancer (15).…”

Section: Introductionmentioning

confidence: 99%

HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma

Tao

Yan

et al. 2017

Oncology Letters

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Abstract. Despite increasing evidence of the involvement of histone deacetylase (HDAC)10 in cancer tumorigenesis, the potential role of HDAC10 in colon cancer remains unclear. Oncomine database analysis revealed that HDAC10 mRNA was significantly upregulated in colon cancer. In an independent cohort, consistent with mRNA expression levels, constitutively high HDAC10 expression was observed in the cytoplasm and nucleus compared with in adjacent normal tissues (cytoplasm, 93.12±12.98 vs. 31.65±26.50%; nucleus, 84.16±19.23 vs. 68.64±19.00%). Cytoplasmic HDAC expression correlated with gender (r=0.265; P<0.05), lymph node metastasis (N stage; r=0.256; P<0.05) and distant metastasis (M stage; r=0.331; P<0.05) in paracarcinoma tissues. Cytoplasmic HDAC10 expression in tumors was not associated with the four DNA mismatch repair genes examined, but was negatively correlated with mutL homolog 1 (MLH1) (r=-0.244; P<0.05), mutS homolog (MSH)2 (r=-0.410; P<0.01) and MSH6 (r=-0.240; P<0.05) in paracarcinoma tissues. Similarly, nuclear HDAC10 expression was negatively correlated with MLH1 expression (r=-0.288; P<0.05). The findings of the current study suggest that HDAC10 expression is associated with good prognosis in colon cancer tissues and poor prognosis in paracarcinoma tissues with a potential involvement in DNA mismatch repair.

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“…Interestingly, ROS induction after HDACi has been frequently described in cancer cells after HDACi. 6,25,38,39 Moreover, potentiation of ROS after combination of HDACi/AZA was suggested as a marker for synergistic cytotoxicity. 40 Our data support previous reports, which found frequent alteration of Trx or TXNIP after HDACi treatment.…”

Section: Discussionmentioning

confidence: 99%

“…40 Our data support previous reports, which found frequent alteration of Trx or TXNIP after HDACi treatment. 6,25,38,39 Interestingly, cancer cells seem to show an upregulation of TXNIP 25,38,39 and downregulation of Trx, 39 whereas normal cells exhibit an increase of Trx 6 after HDACi. In the present study, upregulation of TXNIP was only detectable in OE21 cells but not in OE33 cells.…”

Section: Discussionmentioning

confidence: 99%

Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity

Ahrens

Timme

Ostendorp

et al. 2016

Laboratory Investigation

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We previously showed that histone deacetylase inhibitor (HDACi) and 5-azacytidine (AZA) treatment selectively induced cell death of esophageal cancer cells. The mechanisms of cancer selectivity, however, remained unclear. Here we examined whether the cancer selectivity of HDACi/AZA treatment is mediated by the thioredoxin (Trx) system and reactive oxygen species (ROS) in esophageal cancer cells. For this, we first analyzed human tissue specimens of 37 esophageal cancer patients by immunohistochemistry for Trx, Trx-interacting protein (TXNIP) and Trx reductase (TXNRD). This revealed a loss or at least reduction of nuclear Trx in esophageal cancer cells, compared with normal epithelial cells (Po0.001). Although no differences were observed for TXNIP, TXNRD was more frequently expressed in cancer cells (Po0.001). In the two main histotypes of esophageal squamous cell carcinomas (ESCCs, n = 19) and esophageal adenomcarcinomas (EAC, n = 16), similar Trx, TXNIP and TXNRD expression patterns were observed. Also in vitro, nuclear Trx was only detectable in non-neoplastic Het-1A cells, but not in OE21/ESCC or OE33/EAC cell lines. Moreover, the two cancer cell lines showed an increased Trx activity, being significant for OE21 (P = 0.0237). After treatment with HDACi and/or AZA, ROS were exclusively increased in both cancer cell lines (P = 0.048-0.017), with parallel decrease of Trx activity. This was variably accompanied by increased TXNIP levels upon AZA, MS-275 or MS-275/AZA treatment for 6 or 24 h in OE21, but not in Het-1A or OE33 cells. In summary, this study evaluated Trx and its associated proteins TXNIP and TXNRD for the first time in esophageal cancers. The analyses revealed an altered subcellular localization of Trx and strong upregulation of TXNRD in esophageal cancer cells. Moreover, HDACi and AZA disrupted Trx function and induced accumulation of ROS with subsequent apoptosis in esophageal cancer cells exclusively. Trx function is hence an important cellular mediator conferring non-neoplastic cell resistance for HDACi and/or AZA.

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Inhibition of Histone Deacetylase 10 Induces Thioredoxin-Interacting Protein and Causes Accumulation of Reactive Oxygen Species in SNU-620 Human Gastric Cancer Cells

Cited by 69 publications

References 34 publications

HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats

HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats

HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma

Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity

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