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 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 The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells

2000 ◽  
Vol 21 (7) ◽  
pp. 1403-1409 ◽  
Author(s):  
Erik M. Grossman ◽  
Walter E. Longo ◽  
Ninder Panesar ◽  
John E. Mazuski ◽  
Donald L. Kaminski
Keyword(s):  
Bladder Cancer ◽  
Gall Bladder ◽  
Cancer Cells ◽  
Gall Bladder Cancer ◽  
Bladder Cancer Cells

The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells

2000 ◽  
Vol 21 (7) ◽  
pp. 1403-1409 ◽  
Author(s):  
Erik M. Grossman ◽  
Walter E. Longo ◽  
Ninder Panesar ◽  
John E. Mazuski ◽  
Donald L. Kaminski
Keyword(s):  
Bladder Cancer ◽  
Gall Bladder ◽  
Cancer Cells ◽  
Gall Bladder Cancer ◽  
Bladder Cancer Cells

scholarly journals Low-temperature Plasma Jet Activated Media Induces Apoptosis in Bladder Cancer Cells via the Cytochrome c/caspase 3 Pathway

2021 ◽  
Author(s):  
Hideo Fukuhara ◽  
Endre J. Szili ◽  
Jun-Seok Oh ◽  
Kawada Chiaki ◽  
Shinkuro Yamamoto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ros Production ◽  
Low Temperature Plasma ◽  
Temperature Plasma ◽  
Cycle Arrest ◽  
Mitochondrial Ros ◽  
Bladder Cancer Cells

Abstract Current methods used to treat non-muscle invasive bladder cancer are inadequate due to a high recurrence rate after surgery and occurrence of adverse events such as interstitial pneumonia following intravesical instillation therapy. Low-temperature plasma is a new form of physical therapy that provides a rich source of reactive oxygen species (ROS). Oxidative solutions, created by pre-treatment of aqueous media with plasma before application to target cells, lead to the destruction of cancer cells through oxidative stress pathways. This study focuses on the effects of plasma activated media (PAM) in bladder cancer cells. PAM treatment increases up regulation of p21 and down regulation of Cyclin D and CdK4 leading to cell cycle arrest, and concomitantly depolarises the mitochondrial membrane leading to increased mitochondrial ROS production. Cell cycle arrest and increased mitochondrial ROS production induce apoptosis in bladder cancer cells in vitro and in a bladder cancer tumour in vivo via the pro-apoptotic caspase 3/cytochrome c pathway. These observations highlight the potential of plasma activated solutions as a new adjuvant therapy in the clinical treatment of bladder cancer.

Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

2020 ◽  
Vol 19 (16) ◽  
pp. 2019-2033 ◽  
Author(s):  
Pratibha Pandey ◽  
Mohammad H. Siddiqui ◽  
Anu Behari ◽  
Vinay K. Kapoor ◽  
Kumudesh Mishra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Gall Bladder ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Gall Bladder Cancer ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of 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.

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.

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