N-Acetylcysteine Augments The Cellular Redox Changes and Cytotoxic Activity of Internalized Mycobacterium Bovis in Human Bladder Cancer Cells

Pook, Sim Hwee; Esuvaranathan, Kesavan; Mahendran, Ratha

doi:10.1016/s0022-5347(05)64744-1

Cited by 16 publications

(11 citation statements)

References 24 publications

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“…We previously reported that internalization of BCG correlates with a drop in cellular redox status (8). In this study, we show that by transient transfection of the integrin α5 receptors, we are able to induce cell death in 2 cell lines that are not responsive to BCG cytotoxic effects.…”

Section: Introductionmentioning

confidence: 52%

“…However, BCG-induced killing was blocked by the presence of cycloheximide. This effect indicates that new protein synthesis is required for the induction of necrosis or can be due to the known ability of cycloheximide to reduce cellular reactive oxygen species (ROS) which we had previously shown to correlate with the cytotoxic effect of BCG on cells (8).…”

Section: 67±016 ---------------------------------------------------mentioning

confidence: 99%

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Internalization of Mycobacterium bovis, Bacillus Calmette Guerin, by bladder cancer cells is cytotoxic

Pook

Rahmat²,

Esuvaranathan³

et al. 2007

Oncol Rep

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Abstract. Instillation of Bacillus Calmette Guerin (BCG) into the bladder is the standard treatment for superficial bladder cancer. It leads to a local inflammatory response due to the release of cytokines and influx of immune cells to the tumor site. Although the presence of an intact immune system is an essential criterion for successful therapy, attachment of the bacteria to the bladder urothelial is just as important. The purpose of our study is to determine the role of bacterial internalization by epithelial cells. Transfection of the α5 integrin gene into the BCG unresponsive bladder cancer cell line, RT4, caused an increase in bacterial uptake and also increased cell death. Treatment of cells with cycloheximide did not prevent bacterial internalization but blocked its cytotoxic effect suggesting that unlike cell death, the process of bacterial internalization does not require new protein synthesis. Our data also show that the bacteria secretory products can prevent its own internalization. The extract prepared from lyophilized BCG altered the phosphorylation status of the focal adhesion kinase which is responsible for cellular endocytosis. Therefore, bacterial phosphatases may be present in the bacterial extract. Their activity may inhibit BCG internalization. Thus washing the reconstituted bacteria to remove the enzymes before instillation into the bladder might improve the therapeutic outcome of intravesical BCG therapy.

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Section: Introductionmentioning

confidence: 52%

Section: 67±016 ---------------------------------------------------mentioning

confidence: 99%

Internalization of Mycobacterium bovis, Bacillus Calmette Guerin, by bladder cancer cells is cytotoxic

Pook

Rahmat²,

Esuvaranathan³

et al. 2007

Oncol Rep

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“…Studies have shown that increases in both iNOS and NO are observed in urothelial carcinomas in laboratory models and human bladders following the intravesical instillation of live BCG [4,5,8]. Several prior publications have reported increased bladder tissue expression of iNOS and NO production following the intravesical administration of BCG [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Antioxidants or inducers of iNOS had a positive impact on the in vitro and in vivo effects of BCG respectively [7,8,22]. While one study has suggested that inhibition of iNOS may improve the tumor response to BCG [23], more studies have suggested that increasing iNOS production may be beneficial [7,8,22,24].…”

Section: Discussionmentioning

confidence: 99%

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iNOS expression and NO production contribute to the direct effects of BCG on urothelial carcinoma cell biology

Shah¹,

Zhang²,

Chen³

et al. 2014

Urologic Oncology: Seminars and Original Investigations

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OBJECTIVES-Evidence suggests that oxidative stress occurring as a consequence of inducible nitric oxide synthase/nitric oxide (iNOS/NO) contributes to the biologic effects of Bacille Calmette Guérin (BCG). Objective of the current study is to examine iNOS expression, NO production and the biologic impact of NO, on established intermediate end points for the human urothelial carcinoma cell response to BCG. MATERIALS AND METHODS-Quantitative rt-PCR and real time measurement of NO wasused to assess iNOS and NO production respectively, in two human urothelial carcinoma (UC) cell lines, in response to BCG. The effect of blocking NO production using the specific iNOS inhibitor 1400W was determined for multiple intermediate end points characterizing BCGs direct effects on tumor cell biology. Activation of NF-κB and NRF2 signaling pathways, transactivation of genes including p21, CD54, IL6, IL8, CXCL1, CXCL3, CCL20 and cytotoxicity as measured by vital dye exclusion, lactate dehydrogenase (LDH) release and MTT assay were measured in response to BCG with and without iNOS inhibition.RESULTS-Exposure of UC cells to BCG significantly increased both iNOS expression and NO production. Inhibition of iNOS activity with 1400W significantly inhibited BCG's direct biologic effect on UC cells for all of the end points evaluated.CONCLUSIONS-iNOS expression, NO production and the associated oxidative stress play a central role in the response of UC cells to BCG exposure. Manipulation of oxidative stress may afford an opportunity to enhance the antitumor effects of BCG.

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Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 Murine Bladder Tumor cells

et al. 2004

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Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.

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N-Acetylcysteine Augments The Cellular Redox Changes and Cytotoxic Activity of Internalized Mycobacterium Bovis in Human Bladder Cancer Cells

Cited by 16 publications

References 24 publications

Internalization of Mycobacterium bovis, Bacillus Calmette Guerin, by bladder cancer cells is cytotoxic

Internalization of Mycobacterium bovis, Bacillus Calmette Guerin, by bladder cancer cells is cytotoxic

iNOS expression and NO production contribute to the direct effects of BCG on urothelial carcinoma cell biology

Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 Murine Bladder Tumor cells

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