Up-regulation of connexin 32 gene by 5-aza-2′-deoxycytidine enhances vinblastine-induced cytotoxicity in human renal carcinoma cells via the activation of JNK signalling

Takano, Yasuhiro; Iwata, Hiroki; Yano, Yumiko; Miyazawa, Marta; Virgona, Nantiga; Sato, Hiromi; Ueno, Koichi; Yano, Teruo

doi:10.1016/j.bcp.2010.05.016

Cited by 20 publications

(19 citation statements)

References 27 publications

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“…Increased transcription activity of c-Jun by the JNK activation contributes to the down-regulation of Abcb1b and suppression of ABCB1B expression (Takano et al, 2010). Wild-type p53 is widely known to suppress the expression of Abcb1b through interactions with basal transcription factors, such as TATA-binding protein (Zastawny et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene

Huang

Zhao²,

Shi³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. ATP-binding cassette super family (ABC) proteins are considered key to oncology and pharmacology studies. We examined the effect of benzene on ABC pump protein levels in C57BL/6 mouse bone marrow mononuclear cells. After a 2-week gavage (200 mg/kg, 5 days per week), the number of peripheral leukocytes, lymphocytes and basophils dropped significantly; there was also a significant decrease in MDR1 and MRP1 gene expression. A significant reduction in expression of P-gp was found; however, there was no significant decrease in the expression of MRP1 and NF-κB p65. We conclude that regulation of membrane efflux transport protein could be a factor in benzene hematotoxicity.

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Section: Discussionmentioning

confidence: 99%

Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene

Huang

Zhao²,

Shi³

et al. 2013

Genet. Mol. Res.

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“…We previously reported that the cytotoxicity of VBL was enhanced by pre-treatment with Aza in Caki-1 cells, using an in vitro assay (27). In this study, we investigated the effects of the combined treatment with Aza and VBL in a Caki-1 xenograft model and in a series of RCC cell lines in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…VBL is one of the few classical cytotoxic drugs against RCC (28). We also showed that the combined effect of Aza and VBL was induced via the restoration of the connexin (Cx) 32 gene by demethylation of the promoter region and depression of P-gp expression (27). The gene encoding the gap junction protein, Cx32, is considered to be a tumor-suppressor gene in RCC (29).…”

Section: Introductionmentioning

confidence: 97%

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A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma

et al. 2011

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Abstract. Renal cell carcinoma (RCC) is resistant to chemotherapy partly due to the overexpression of the P-glycoprotein. Several tumor suppressor genes have been reported to be silenced by hypermethylation of the promoter region in RCC. We recently reported that the in vitro cytotoxicity of vinblastine (VBL) was enhanced by pre-treatment with the demethylating agent, 5-aza-2'-deoxycytidine (Aza), in the RCC cell line, Caki-1. In this study, we investigated the combined effect of Aza and VBL in a Caki-1 xenograft model and in other RCC cell lines in vitro. In the xenograft model, tumor volume and weight were significantly suppressed in the co-treatment group, compared to the control, and the expressions of P-glycoprotein, Bcl-2 and cyclin B1 were reduced. Thus, this combined effect could be mediated by the accumulation of intracellular VBL and the enhancement of apoptosis and cell cycle arrest. Moreover, the cytotoxicity of VBL was enhanced in vitro in three RCC cell lines by Aza treatment. These findings suggest that the combination treatment with Aza and VBL is effective against RCC.

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“…5,6) It is well known that dietary intake of fruit or herbal health drinks containing sufficient flavanoids will reduce the occurrence risk of cancer (e.g. breast, lung and colon).…”

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Total Flavonoids of Litsea Coreana Enhance the Cytotoxicity of Oxaliplatin by Increasing Gap Junction Intercellular Communication

Dong

et al. 2014

Biological & Pharmaceutical Bulletin

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Oxaliplatin is widely used in the treatment of variety of cancers, including cancer of the testis and colorectum. Gap junctions (GJs) can amplify the cytotoxicity of antinoeoplastic drugs through the bystander effect in different cancer cells. In this study, we demonstrate that total flavonoids of litsea coreana (TFLC), one extract from the dried leaves of litsea coreana leve, increase the cytotoxicity of oxaliplatin in mouse testicular cancer I-10 cells. We found that cell survival was substantially decreased only when functional GJs formed in I-10 cells. TFLC increased oxaliplatin cytotoxity (inducing cell death and apoptosis) by enhancing gap junction intercellular communication (GJIC) through elevated Cx43 protein expression. Furthermore, apoptosis-related protein (Bax, Bcl-2, caspase-3/9) results showed that the Bax/Bcl-2 ratio and activated caspase-3/9 increased when TFLC was used compared with treatment with oxaliplatin alone, which suggests that the mechanism of increased oxaliplatin-induced apoptosis was through the mitochondrial pathway. These results demonstrate that TFLC can enhance the cytotoxicity of oxaliplatin, and that these processes may be regulated in testicular tumor cells through GJ-mediated regulation of tumor cell apoptosis.Key words litsea coreana; gap junction; apoptosis; oxaliplatin Gap junctions (GJs) are intercellular channels that connect the cytoplasm of adjacent cells. They have vital implication in regulation of homeostasis, morphogenesis, cell differentiation, and growth control in multicellular organisms. GJs are consisted with core protein-connexin. A considerable number of studies have established that GJs are decreased in variety of tumors.1-4) Furthermore, enhancement of GJs increases cytotoxicity during cancer chemotherapy and radiotherapy. 5,6) It is well known that dietary intake of fruit or herbal health drinks containing sufficient flavanoids will reduce the occurrence risk of cancer (e.g. breast, lung and colon). Total flavonoids of litsea coreana (TFLC), one of the flavonoids, is the key pharmacologically active constituents extracted from litsea coreana leve which is a traditional Chinese medicine. TFLC primarily consists of five flavonoids, identified as quercetin-3-β-D-galactoside, quercetin-3-β-D-glucoside, kaempferol-3-β-D-glucoside, kaempferol-3-β-D-galactoside and catechin. Oxaliplatin (OHP) [1,2-diaminocyclohexane (trans-1) oxolatoplatinum(II)], a related platinum based chemotherapeutic agent, reacting with GC-rich areas of DNA, forming both intrastrand and interstrand cross-links, leading to G2 arrest and to apoptosis or necrosis.10) It is commonly used in the treatement of testicular cancer. Wang et al. also demonstrated that the cytotoxicity of oxaliplatin was increased in the presence of GJ and increasing GJ function enhanced cytotoxicity of oxaliplatin in the cells with functional GJ.11) And a simple inference from these reports is that induction of apoptotic or necrotic processes in one cell can cause a molecular "death signal" to be transmitted to neig...

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Up-regulation of connexin 32 gene by 5-aza-2′-deoxycytidine enhances vinblastine-induced cytotoxicity in human renal carcinoma cells via the activation of JNK signalling

Cited by 20 publications

References 27 publications

Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene

Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene

A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma

Total Flavonoids of Litsea Coreana Enhance the Cytotoxicity of Oxaliplatin by Increasing Gap Junction Intercellular Communication

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