Oxidative Stress Sensitizes Bladder Cancer Cells to TRAIL Mediated Apoptosis by Down-Regulating Anti-Apoptotic Proteins

Background/Aims: Cancer is the second most deadly disease in the world. The bladder cancer is one of the most aggressive types and shows a continuous increase in the number of cases. The use of bacteria as live vectors to deliver molecules directly to the tumor is a promising tool and has been used as an adjuvant treatment against several types of cancer. The aim of this study was to investigate the antitumor effect of Interleukin 2 (IL-2), TNF-related apoptosis-inducing ligand (TRAIL) and protein MIX against murine bladder cancer cells, lineage MB49. Methods: The attenuated Salmonella strain SL3261 was transformed by inserting the IL-2 and TRAIL genes. The effects of proteins on cell viability (MTT method), cell morphology (optical microscopy), cell recovery (clonogenic assay), cell membrane (lactate dehydrogenase release - LDH), on oxidative stress pathway (levels of nitric oxide, NO) and apoptosis (flow cytometry and high resolution epifluorescence images) were evaluated at intervals of 24 and 48 hours of action. Results: The results showed that there was a decrease in cell viability via damage to the cell membrane, alteration of cell morphology, non-recovery of cells, increase in the production of NO and incubate for of cells in the state of apoptosis in the two periods analyzed. Conclusion: The data presented suggest that IL-2, TRAIL and their MIX proteins in MB49 cells have cytotoxic potential and that this is associated with oxidative stress and apoptosis pathways. These results may contribute to the development of new therapeutic strategies for bladder cancer.

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Ailanthone increases oxidative stress in CDDP-resistant ovarian and bladder cancer cells by inhibiting of Nrf2 and YAP expression through a post-translational mechanism

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2020.02.021 ◽

2020 ◽

Vol 150 ◽

pp. 125-135 ◽

Cited By ~ 3

Author(s):

Marie Angèle Cucci ◽

Margherita Grattarola ◽

Chiara Dianzani ◽

Giovanna Damia ◽

Francesca Ricci ◽

...

Keyword(s):

Oxidative Stress ◽

Bladder Cancer ◽

Cancer Cells ◽

Bladder Cancer Cells

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Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription

International Journal of Molecular Sciences ◽

10.3390/ijms21051710 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1710 ◽

Cited By ~ 3

Author(s):

Sang-Seok Oh ◽

Ki Won Lee ◽

Hamadi Madhi ◽

Jin-Woo Jeong ◽

Soojong Park ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Promoter Activity ◽

Tumor Therapy ◽

Cancer Drugs ◽

Anti Cancer ◽

Bladder Cancer Cells ◽

Mdr1 Expression ◽

Apoptotic Proteins ◽

Mdr1 Promoter

Tumor cell resistance to anti-cancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin in T24R2 cells, a T24-derived cell line. Treatment with cordycepin or cisplatin (2 μg/mL) alone failed to induce cell death in T24R2 cells, but combination treatment with these drugs significantly induced apoptosis through mitochondrial pathways, including depolarization of mitochondrial membranes, decrease in anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, and increase in pro-apoptotic proteins Bak and Bax. High expression levels of MDR1 were the cause of cisplatin resistance in T24R2 cells, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on transcription factor Ets-1 in T24R2 cells. Although correlation exists between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr38 phosphorylated form (pThr38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 levels and reduced MDR1 transcription, probably through its effects on PI3K signaling, inducing the resensitization of T24R2 cells to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of cancer in patients with resistance to anti-cancer drugs.

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Dose-dependent effect of Resveratrol on bladder cancer cells: Chemoprevention and oxidative stress

Maturitas ◽

10.1016/j.maturitas.2012.02.004 ◽

2012 ◽

Vol 72 (1) ◽

pp. 72-78 ◽

Cited By ~ 27

Author(s):

Bianca Stocco ◽

Karina Toledo ◽

Mirian Salvador ◽

Michele Paulo ◽

Natália Koyama ◽

...

Keyword(s):

Oxidative Stress ◽

Bladder Cancer ◽

Cancer Cells ◽

Dependent Effect ◽

Bladder Cancer Cells ◽

Dose Dependent ◽

Dose Dependent Effect ◽

And Oxidative Stress

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OXIDATIVE STRESS AND REGULATION OF INVASIVE PHENOTYPE IN BLADDER CANCER CELLS

The Journal of Urology ◽

10.1016/s0022-5347(08)60769-7 ◽

2008 ◽

Vol 179 (4S) ◽

pp. 265-265

Author(s):

James Belarmino ◽

J Andre Melendez ◽

Xio-Fang Ha ◽

Badar M Mian

Keyword(s):

Oxidative Stress ◽

Bladder Cancer ◽

Cancer Cells ◽

Invasive Phenotype ◽

Bladder Cancer Cells

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Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

Antioxidants ◽

10.3390/antiox10071063 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1063

Author(s):

Tsu-Ming Chien ◽

Kuang-Han Wu ◽

Ya-Ting Chuang ◽

Yun-Chiao Yeh ◽

Hui-Ru Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Bladder Cancer ◽

Cancer Cells ◽

Withaferin A ◽

Heme Oxygenase 1 ◽

Dependent Manner ◽

Dna Damages ◽

Bladder Cancer Cells ◽

Stress Dependent

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

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