scholarly journals Hypofractionated Radiation Induced the Immunogenic Death of Bladder Cancer Cells Leading to the Immune Sensitization of Dendritic Cells

2021 ◽  
Author(s):  
Xianlin Zeng ◽  
Zhonghui Cui ◽  
yun wang ◽  
Jin Chen ◽  
Fuzhou Tang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Immune Response ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Hypofractionated Radiotherapy ◽  
Bladder Cancer Cells ◽  
M Phase ◽  
Radiation Induced ◽  
Hypofractionated Radiation ◽  
Apoptosis Level

Abstract Purpose Radiotherapy is a commonly used method in the treatment of bladder cancer (BC). Radiation induced immunogenic death (ID) and antitumor immune response are related to the prognosis of radiotherapy. As the most powerful antigen-presenting cell in the body, the role of dendritic cells (DCs) is not very clear. Methods Apoptosis level, cell cycle analysis and expression levels of high mobility group protein 1 (HMGB1), calreticulin (CRT) and heat shock protein 70 (HSP70) were performed for bladder cancer cells after hypofractionated radiotherapy. The effects of the conditioned media on DCs for antitumor immune response activation were studied as well. Results The significantly increased apoptosis level, G2/M phase cell cycle arrest and significantly increased HMGB1, CRT and HSP70 expressions, and increased secretion of CCL5 and CCL21 in the supernatant of bladder cancer cells after hypofractionated radiotherapy. The expression of CD80, CD86, CCR5 and CCR7 on DCs was upregulated in the conditioned media of bladder cancer cells after hypofractionated radiotherapy. Conclusion Hypofractionated radiation blocked the cell cycle of BC cells in the G2/M phase and induced ID occurrence, resulting in DCs immune sensitization, which is of great clinical significance in understanding the radiotherapy of BC and the immunoregulation function of DCs.

scholarly journals Anti-Proliferative and Pro-Apoptotic Effects of Licochalcone A through ROS-Mediated Cell Cycle Arrest and Apoptosis in Human Bladder Cancer Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3820 ◽  
Author(s):  
Su Hyun Hong ◽  
Hee-Jae Cha ◽  
Hyun Hwang-Bo ◽  
Min Yeong Kim ◽  
So Young Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Cycle Arrest ◽  
Bladder Cancer Cells ◽  
M Phase ◽  
Human Bladder Cancer Cells

Licochalcone A (LCA) is a chalcone that is predominantly found in the root of Glycyrrhiza species, which is widely used as an herbal medicine. Although previous studies have reported that LCA has a wide range of pharmacological effects, evidence for the underlying molecular mechanism of its anti-cancer efficacy is still lacking. In this study, we investigated the anti-proliferative effect of LCA on human bladder cancer cells, and found that LCA induced cell cycle arrest at G2/M phase and apoptotic cell death. Our data showed that LCA inhibited the expression of cyclin A, cyclin B1, and Wee1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdc2 and Cdk2. LCA activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, LCA increased the Bax/Bcl-2 ratio, and reduced the integrity of mitochondria, which contributed to the discharge of cytochrome c from the mitochondria to the cytoplasm. Moreover, LCA enhanced the intracellular levels of reactive oxygen species (ROS); however, the interruption of ROS generation using ROS scavenger led to escape from LCA-mediated G2/M arrest and apoptosis. Collectively, the present data indicate that LCA can inhibit the proliferation of human bladder cancer cells by inducing ROS-dependent G2/M phase arrest and apoptosis.

Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

2019 ◽  
Vol 19 (6) ◽  
pp. 826-837 ◽  
Author(s):  
Pratibha Pandey ◽  
Preeti Bajpai ◽  
Mohammad H. Siddiqui ◽  
Uzma Sayyed ◽  
Rohit Tiwari ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Gall Bladder ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Annexin V ◽  
Gall Bladder Cancer ◽  
Apoptosis Induction ◽  
Bladder Cancer Cells ◽  
Hoechst Staining

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

scholarly journals Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1381
Author(s):  
So Young Kim ◽  
Hyun Hwangbo ◽  
Min Yeong Kim ◽  
Seon Yeong Ji ◽  
Da Hye Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Cycle Arrest ◽  
Bladder Cancer Cells ◽  
Induced Apoptosis ◽  
Human Bladder Cancer Cells

Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells.

scholarly journals Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 369
Author(s):  
Jochen Rutz ◽  
Sebastian Maxeiner ◽  
Eva Juengel ◽  
Felix K.-H. Chun ◽  
Igor Tsaur ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Olive Mill Wastewater ◽  
Mtor Signaling ◽  
Beneficial Effects ◽  
Cycle Arrest ◽  
Bladder Cancer Cells ◽  
Olive Mill

Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy.

UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53

2020 ◽  
Vol 27 (12) ◽  
pp. 934-947
Author(s):  
Yexiang Huang ◽  
Yuyan Zhu ◽  
Zhe Zhang ◽  
Zhenhua Li ◽  
Chuize Kong
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Phase Arrest ◽  
Bladder Cancer Cells ◽  
M Phase

scholarly journals The Antitumor Effect of Curcumin in Urothelial Cancer Cells Is Enhanced by Light Exposure In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Frederik Roos ◽  
Katherina Binder ◽  
Jochen Rutz ◽  
Sebastian Maxeiner ◽  
August Bernd ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Visible Light ◽  
Cancer Cells ◽  
Cell Lines ◽  
Light Exposure ◽  
Bladder Cancer Cells

The natural compound curcumin exerts antitumor properties in vitro, but its clinical application is limited due to low bioavailability. Light exposure in skin and skin cancer cells has been shown to improve curcumin bioavailability; thus, the object of this investigation was to determine whether light exposure might also enhance curcumin efficacy in bladder cancer cell lines. RT112, UMUC3, and TCCSUP cells were preincubated with low curcumin concentrations (0.1-0.4μg/ml) and then exposed to 1.65 J/cm2visible light for 5 min. Cell growth, cell proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins along with acetylation of histone H3 and H4 were investigated. Though curcumin alone did not alter cell proliferation or apoptosis, tumor cell growth and proliferation were strongly blocked when curcumin was combined with visible light. Curcumin-light caused the bladder cancer cells to become arrested in different cell phases: G0/G1 for RT112, G2/M for TCCSUP, and G2/M- and S-phase for UMUC3. Proteins of the Cdk-cyclin axis were diminished in RT112 after application of 0.1 and 0.4μg/ml curcumin. Cell cycling proteins were upregulated in TCCSUP and UMUC3 in the presence of 0.1μg/ml curcumin-light but were partially downregulated with 0.4μg/ml curcumin. 0.4μg/ml (but not 0.1μg/ml) curcumin-light also evoked late apoptosis in TCCSUP and UMUC3 cells. H3 and H4 acetylation was found in UMUC3 cells treated with 0.4μg/ml curcumin alone or with 0.1μg/ml curcumin-light, pointing to an epigenetic mechanism. Light exposure enhanced the antitumor potential of curcumin on bladder cancer cells but by different molecular action modes in the different cell lines. Further studies are necessary to evaluate whether intravesical curcumin application, combined with visible light, might become an innovative tool in combating bladder cancer.

scholarly journals Correction: UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53

2021 ◽  
Author(s):  
Yexiang Huang ◽  
Yuyan Zhu ◽  
Zhe Zhang ◽  
Zhenhua Li ◽  
Chuize Kong
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Phase Arrest ◽  
Bladder Cancer Cells ◽  
M Phase

scholarly journals Anticancer and apoptosis-inducing effects of curcumin against gall bladder carcinoma

2018 ◽  
Vol 9 (1) ◽  
pp. 68 ◽  
Author(s):  
Pratibha Pandey ◽  
Uzma Sayyed ◽  
Rohit Tiwari ◽  
Neelam Pathak ◽  
Mohammad Haris Siddiqui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Gall Bladder ◽  
Cancer Cells ◽  
Bladder Carcinoma ◽  
Caspase 3 ◽  
Gall Bladder Cancer ◽  
Dependent Manner ◽  
Gall Bladder Carcinoma ◽  
Bladder Cancer Cells

Curcumin, the primary bioactive component isolated from turmeric, has been shown to possess variety of biologic functions including anti-cancer activity. However, meticulous mechanism of the curcumin in gall bladder cancer has not been explored yet. Therefore, in our study, we elucidated the mechanism of the anticancer action of curcumin against human gall bladder cancer cells. It was found that the curcumin treated GBC cells decreased cell viability in a dose and time-dependent manner. Nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation confirmed the apoptotic induction due to anti-proliferative action of curcumin. Furthermore, curcumin induced disruption in the mitochondrial membrane potential and increased reactive oxygen species generation which has not yet been reported in earlier studies of curcumin with gall bladder cancer. Moreover, curcumin-induced apoptosis of gall bladder cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To the best part of my knowledge, this study has established curcumin as one of the promising chemotherapeutic agent against gall bladder carcinoma. Thus the present study explored a novel mechanism explaining the anti cancerous effects of curcumin, and may provide an alternative therapeutic approach which can overcome the side effects of chemotherapy. Keywords: Gall bladder carcinoma Curcumin; Cell cycle analysis; Caspase-3; Apoptosis

scholarly journals Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells

2020 ◽  
Vol 21 (11) ◽  
pp. 4026 ◽  
Author(s):  
Saira Justin ◽  
Jochen Rutz ◽  
Sebastian Maxeiner ◽  
Felix K.-H. Chun ◽  
Eva Juengel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Mtor Inhibitor ◽  
Down Regulation ◽  
Resistance Development ◽  
Bladder Cancer Cells

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 µM) alone or in combination. Cell growth, proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins were evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Short-term application of SFN and/or everolimus resulted in significant tumor growth suppression, with additive inhibition on clonogenic tumor growth. Long-term everolimus treatment resulted in resistance development characterized by continued growth, and was associated with elevated Akt-mTOR signaling and cyclin-dependent kinase (CDK)1 phosphorylation and down-regulation of p19 and p27. In contrast, SFN alone or SFN+everolimus reduced cell growth and proliferation. Akt and Rictor signaling remained low, and p19 and p27 expressions were high under combined drug treatment. Long-term exposure to SFN+everolimus also induced acetylation of the H3 and H4 histones. Phosphorylation of CDK1 was diminished, whereby down-regulation of CDK1 and its binding partner, Cyclin B, inhibited tumor growth. In conclusion, the addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

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