scholarly journals Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1607
Author(s):  
Ana T. P. C. Gomes ◽  
Rosa Fernandes ◽  
Carlos F. Ribeiro ◽  
João P. C. Tomé ◽  
Maria G. P. M. S. Neves ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Heck Reaction ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Porphyrin Derivatives ◽  
Biological Studies ◽  
Bladder Cancer Cells ◽  
Photodynamic Activity

Novel triazole-porphyrin derivatives (TZ-PORs) were synthesized through the Heck reaction and then incorporated into polyvinylpyrrolidone (PVP) micelles. After verifying that this incorporation did not compromise the photophysical and chemical features of TZ-PORs as photosensitizers, the phototoxicity of the formulations towards cancer cells was screened. Biological studies show high photodynamic activity of all PVP-TZ-POR formulations against a bladder cancer cell line with a particular highlight to PVP-TZ-POR 7e and 7f that are able to significantly reduce HT-1376 cell viability, while they had no effect on control ARPE-19 cells.

Effect of defective ERCC2 on cisplatin and ionizing radiation (IR) sensitivity in bladder cancer cells.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 333-333
Author(s):  
Qiang Li ◽  
Andrew Bell ◽  
Emmet Jordan ◽  
Sizhi Paul Gao ◽  
Jennifer Ma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Bladder Cancer Cells ◽  
Bladder Sparing ◽  
Mutant Cells

333 Background: Genetic alterations within ERCC2 correlate with extraordinary responses to neoadjuvant cisplatin-based chemotherapy and bladder-sparing ionizing radiation (IR) in muscle-invasive bladder cancer (MIBC). Two studies correlated ERCC2 mutations with pathologic response to chemotherapy and improved disease-free and bladder intact survival following trimodality therapy. We sought to characterize the biological significance of these mutations in bladder cancer cells using CRISPR/Cas9-mediated ablation of ERCC2 function. Methods: The ERCC2 T484A/M point mutation was the most common alteration (4 of 36 patients) within a prospectively collected cohort of 299 bladder cancer patients sequenced at our institution. We infected the ERCC2 wild-type KU19-19 bladder cancer cell line with a CRISPR/Cas9 lentivirus targeting residues 481-487 of ERCC2 and identified a cell clone harboring an ERCC2 in-frame deletion (M483_T484del). Following exposure to cisplatin and IR, cell viability was examined using Cell-titer Glo and clonogenic assays. Apoptosis was gauged by subG1 cell fraction measurement by flow cytometry. Results: ERCC2 mutant cells exhibited significantly increased cisplatin sensitivity compared to parental cells (IC50 0.3uM vs 2.0uM, p < 0.0001). Cisplatin treatment after 48 hours resulted in increased apoptosis in ERCC2 mutant vs parental cells (sub-G1 fraction 52% vs 16%, p = 0.01). ERCC2 mutant cells were more sensitive to combined IR (2 Gy) and cisplatin (1uM) compared to parental cells (SF2Gy (surviving fraction) 17 % vs 60%). Conclusions: ERCC2 mutations enhance cisplatin and IR sensitivity in a bladder cancer cell line model. ERCC2 alterations are likely the genetic basis for extraordinary response to cisplatin chemotherapy and IR in MIBC patients. Prospective genetic sequencing may help select ERCC2 mutant MIBC patients who are most likely to respond to chemotherapy or trimodality bladder-sparing therapy.

scholarly journals Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiawa Mao ◽  
Nanzhang ◽  
Jiaquao Xiao ◽  
Huifeng Wu ◽  
Kefeng Ding
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Cancer Cell Line ◽  
Hypoxic Condition ◽  
Underlying Mechanism ◽  
Bladder Cancer Cell Line ◽  
Hypoxic Conditions ◽  
Bladder Cancer Cells ◽  
Autophagy Pathway

Purpose. To investigate the effect of hypoxia on chemoresistance and the underlying mechanism in bladder cancer cells. Methods. BIU-87 bladder cancer cell line was treated with cisplatin under hypoxic and normoxic conditions and tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting. All the data were expressed as mean ± standard   error from three independent experiments and analyzed by multiple t -tests. Results. Apoptosis of bladder cancer cells caused by cisplatin was attenuated in hypoxic conditions. Hypoxia enhanced autophagy caused by cisplatin. The autophagy inhibitor and HIF-1α inhibitor can reverse the chemoresistance in hypoxic condition. Apoptosis and autophagy of bladder cancer cells were downregulated by HIF-1α inhibitor YC-1. Hypoxia-induced autophagy enhanced chemoresistance to cisplatin via the HIF-1 signaling pathway. Conclusion. Resistance to cisplatin in BIU-87 bladder cancer cells under hypoxic conditions can be explained by activation of autophagy, which is regulated by HIF-1α-associated signaling pathways. The hypoxia–autophagy pathway may be a target for improving the efficacy of cisplatin chemotherapy in bladder cancer.

scholarly journals Effects of the Zinc Finger Protein 485 (ZNF485) on the Proliferation, Metastasis and Invasion of Bladder Cancer Cells

2021 ◽  
pp. 1-8
Author(s):  
Dabing Huang ◽  
Yiao Tan ◽  
Fangfang Zhao ◽  
Chunbao Zang ◽  
Shuhan Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Finger Protein ◽  
Bladder Cancer Cells ◽  
New Gene

Objectives: Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. The limited progress on the diagnostics and treatment largely impedes the survival of bladder cancer patients. Methods: Potential therapeutic biomarkers are urgently needed for future clinic treatment. We performed the RNA-seq assays and identified a new gene zinc finger protein 485, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients. Results: We found that inhibition of ZNF485 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation and promotes the apoptosis of cancer cells. Furthermore, the wound healing and invasion assays showed that down-regulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-siRNA transfected obviously inhibited tumor growth in nude mice. Conclusion: Taken together, the results provide evidence that ZNF485 is involved in the tumorigenesis of bladder cancer, which might be a potential therapeutic biomarker for the treatment of this disease.

scholarly journals Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells

2021 ◽  
Vol 55 (4) ◽  
pp. 460-476
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cell Membrane ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Antitumor Effect ◽  
Interleukin 2 ◽  
Continuous Increase ◽  
Bladder Cancer Cells

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.

Possibilities of in silico estimations for the development of pharmaceutical composition phytoladaptogene cytotoxic for bladder cancer cells

2021 ◽  
Vol 67 (3) ◽  
pp. 278-288
Author(s):  
N.S. Ionov ◽  
M.A. Baryshnikova ◽  
E.V. Bocharov ◽  
P.V. Pogodin ◽  
A.A. Lagunin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
In Silico ◽  
Caspase 3 ◽  
Bladder Cancer Cell Line ◽  
Wide Range ◽  
Bladder Cancer Cells ◽  
Pharmaceutical Composition

Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: — the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.

scholarly journals Unraveling the Photodynamic Activity of Cationic Benzoporphyrin-Based Photosensitizers against Bladder Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5312
Author(s):  
Ana T. P. C. Gomes ◽  
M. Graça P. M. S. Neves ◽  
Rosa Fernandes ◽  
Carlos F. Ribeiro ◽  
José A. S. Cavaleiro ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bladder Cancer ◽  
Singlet Oxygen ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Oxygen Formation ◽  
Bladder Cancer Cells ◽  
Photodynamic Activity ◽  
Singlet Oxygen Formation

In this study, we report the preparation of new mono-charged benzoporphyrin complexes by reaction of the appropriate neutral benzoporphyrin with (2,2′-bipyridine)dichloroplatinum(II) and of the analogs’ derivatives synthesized through alkylation of the neutral scaffold with iodomethane. All derivatives were incorporated into polyvinylpyrrolidone (PVP) micelles. The ability of the resultant formulations to generate reactive oxygen species was evaluated, mainly the singlet oxygen formation. Then, the capability of the PVP formulations to act as photosensitizers against bladder cancer cells was assessed. Some of the studied formulations were the most active photosensitizers causing a decrease in HT-1376 cells’ viability. This creates an avenue to further studies related to bladder cancer cells.

scholarly journals Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5658
Author(s):  
Kyoung-Hwa Lee ◽  
Byung-Chan Kim ◽  
Seung-Hwan Jeong ◽  
Chang Wook Jeong ◽  
Ja Hyeon Ku ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Histone Demethylase ◽  
Bladder Cancer Cell ◽  
Bladder Cancer Cell Line ◽  
Mouse Xenograft Model ◽  
Bladder Cancer Cells

Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer.

scholarly journals A Microfluidic Detection System for Bladder Cancer Tumor Cells

Micromachines ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 871
Author(s):  
Shuxing Lv ◽  
Jinwei Yu ◽  
Yan Zhao ◽  
Hongxiang Li ◽  
Fang Zheng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Diagnosis ◽  
Detection System ◽  
Cell Number ◽  
Bladder Cancer Cell Line ◽  
Bladder Cancer Cells ◽  
Diluted Solution

The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine interferes with the recognition of tumor cells. In this paper, a technique for detecting cancer cells in urine based on microfluidics provides a novel approach to bladder cancer diagnosis. The bladder cancer cell line (T24) and MeT-5A were used as positive bladder tumor cells and non-tumor cells, respectively. The practicality of the tumor cell detection system based on microfluidic cell chip detection technology is discussed. The tumor cell (T24) concentration was around 1 × 104 to 300 × 104 cells/mL. When phosphate buffer saline (PBS) was the diluted solution, the tumor cell detected rate was 63–71% and the detection of tumor cell number stability (coefficient of variation, CV%) was 6.7–4.1%, while when urine was the diluted solution, the tumor cell detected rate was 64–72% and the detection of tumor cell number stability (CV%) was 6.3–3.9%. In addition, both PBS and urine are tumor cell dilution fluid solutions. The sample was analyzed at a speed of 750 microns per hour. Based on the above experiments, a system for detecting bladder cancer cells in urine by microfluidic analysis chip technology was reported. The rate of recognizing bladder cancer cells reached 68.4%, and the speed reached 2 mL/h.

scholarly journals Aloperine prevents hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells through regulating the mTOR/p70S6K/4E-BP1 pathway

2020 ◽  
Author(s):  
Weiling Lv ◽  
Qian Liu ◽  
Jihong An ◽  
Xiaoyong Song
Keyword(s):  
Bladder Cancer ◽  
Western Blot ◽  
Cell Viability ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
T24 Cells ◽  
Bladder Cancer Cells

Abstract Background: Aloperine (ALO), a novel active alkaloid extracted from S. alopecuroide, has been reported to possess anti-tumor effect. However, its potential effect on bladder cancer remains unknown. Therefore, the objective of this study was to investigate the effect of ALO bladder cancer cells under hypoxia condition.Methods: Human bladder cancer cell line T24 cells were treated with different concentrations of ALO and maintained in hypoxic condition for 12, 24, or 48 h. MTT assay was performed to detect cell viability. Transwell assay was performed to detect cell migration and invasion. Epithelial-mesenchymal transition (EMT) was evaluated by detecting the expression levels of E-cadherin, N-cadherin, and vimentin using western blot. The mRNA and protein levels of HIF-1α, snail, slug, and twist1 were measured using qRT-PCR and western blot. The expression levels of mTOR/p70S6K/4E-BP1 pathway-related proteins were detected using western blot.Results: Our results showed that ALO inhibited the cell viability of T24 cells cultured in hypoxia condition. ALO also attenuated hypoxia-induced migration and invasion of T24 cells. We also found that ALO treatment caused a significant increase in E-cadherin expression and decreases in N-cadherin and vimentin expressions. Besides, ALO dose-dependently inhibited the expressions of EMT inducers including snail, slug, and twist1 both in mRNA and protein levels in T24 cells induced by hypoxia. Furthermore, ALO significantly inhibited HIF-1α protein synthesis and phosphorylation of mTOR, as well 4E-BP1 and p70S6K in hypoxia-induced T24 cells.Conclusion: These results indicated that ALO exerted anti-tumor effect on bladder cancer in vitro via inhibiting the activation of mTOR/p70S6K/4E-BP1 pathway.

scholarly journals Downregulated XPA promotes carcinogenesis of bladder cancer via impairment of DNA repair

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769167 ◽  
Author(s):  
Yi Zhi ◽  
Huixiang Ji ◽  
Jinhong Pan ◽  
Peng He ◽  
Xiaozhou Zhou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dna Repair ◽  
Cell Viability ◽  
Cancer Susceptibility ◽  
Excision Repair ◽  
Cancer Cell Line ◽  
Strand Break ◽  
Bladder Cancer Cell Line ◽  
Bladder Tissue ◽  
High Mutation Frequency

Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration. XPA reduction increased cell viability of a bladder cancer cell line RT4, while XPA re-expression decreased the cell viability of RT4 cells. Since high mutation frequency is the basis of mutations of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility, our study suggests that downregulated XPA may promote carcinogenesis of bladder cancer via impairment of DNA repair.

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