scholarly journals Isoquercitrin inhibits bladder cancer progression in vivo and in vitro by regulating the PI3K/Akt and PKC signaling pathways

2016 ◽  
Vol 36 (1) ◽  
pp. 165-172 ◽  
Author(s):  
FENG CHEN ◽  
XIAOCHI CHEN ◽  
DEYONG YANG ◽  
XIANGYU CHE ◽  
JIANBO WANG ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Pkc Signaling

scholarly journals Anti-Cancer Properties of Theaflavins

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 987
Author(s):  
Eric J. O’Neill ◽  
Deborah Termini ◽  
Alexandria Albano ◽  
Evangelia Tsiani
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
B Cell Lymphoma ◽  
Black Tea ◽  
Phosphorylated Akt ◽  
Phenolic Components ◽  
Anti Cancer

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.

scholarly journals Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sareshma Sudhesh Dev ◽  
Syafiq Asnawi Zainal Abidin ◽  
Reyhaneh Farghadani ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Surface Proteins ◽  
Downstream Signaling ◽  
Anti Cancer ◽  
Rtk Inhibitors

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

scholarly journals Independence of HIF1a and androgen signaling pathways in prostate cancer

2019 ◽  
Author(s):  
Maxine GB Tran ◽  
Becky AS Bibby ◽  
Lingjian Yang ◽  
Franklin Lo ◽  
Anne Warren ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Promote Tumor Growth ◽  
Elevated Expression

AbstractAndrogen signaling drives prostate cancer progression and is a therapeutic target. Hypoxia/HIF1a signaling is associated with resistance to hormone therapy and a poor prognosis in patients treated with surgery or radiotherapy. It is not known whether the pathways operate in cooperation or independently. Using LNCaP cells with and without stable transfection of a HIF1a expression vector, we show that combined AR and HIF1a signaling promotes tumor growth in vitro and in vivo, and the capacity of HIF1a to promote tumor growth in the absence of endogenous androgen in vivo. Gene expression analysis identified 7 genes that were upregulated by both androgen and HIF1a. ChIP-Seq analysis showed that the AR and HIF/hypoxia signaling pathways function independently regulating the transcription of different genes with few shared targets. In clinical datasets elevated expression of 5 of the 7 genes was associated with a poor prognosis. Our findings suggest that simultaneous therapeutic inhibition of AR and HIF1a signaling pathways should be explored as a potential therapeutic strategy.

scholarly journals CircZNF609 Promotes Bladder Cancer Progression and Inhibits Cisplatin Sensitivity via miR-1200/CDC25B Pathway

2021 ◽  
Author(s):  
Dexiang Feng ◽  
Jiancheng Lv ◽  
Kai Li ◽  
Qiang Cao ◽  
Jie Han ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Online Databases ◽  
Cisplatin Sensitivity ◽  
Cisplatin Chemoresistance

Abstract Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 has been shown to act as an oncogene in a variety of solid tumors and may serve as a novel biomarker for tumor diagnosis and treatment. However, the underlying role and mechanism of circZNF609 in bladder cancer (BCa) development and cisplatin chemosensitivity were unknown. Quantitative real-time PCR (qRT-PCR) was applied to determine the expression of circZNF609, microRNA 1200 (miR-1200) and CDC25B in BCa cells and tissues. Western blot was used to detect the protein level of CDC25B. Functional assays in vitro and in vivo were conducted to investigate the effects of circZNF609 on tumor development and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200 and CDC25B. Dual luciferase reporter assay, RNA pull-down assay and RNA fluorescence in situ hybridization (FISH) were applied to confirm the mechanism. CircZNF609 expression was significantly up-regulated in BCa cell lines and tissues. Increased expression of circZNF609 was related to a worse survival in BCa patients. In vitro and in vivo, enforced-expression of circZNF609 enhanced BCa cells proliferation, migration and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to serve as a new diagnostic biomarker and therapeutic target for BCa patients.

scholarly journals Deficiency of Mettl3 in Bladder Cancer Stem Cells Inhibits Bladder Cancer Progression and Angiogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ganping Wang ◽  
Yarong Dai ◽  
Kang Li ◽  
Maosheng Cheng ◽  
Gan Xiong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Messenger Rna ◽  
Conditional Knockout ◽  
Stem Cell Population ◽  
Protein Levels ◽  
Rna Immunoprecipitation ◽  
Endothelial Growth Factor

RNA N6-methyladenosine is a key step of posttranscriptional modulation that is involved in governing gene expression. The m6A modification catalyzed by Mettl3 has been widely recognized as a critical epigenetic regulation process for tumorigenic properties in various cancer cell lines, including bladder cancer. However, the in vivo function of Mettl3 in bladder cancer remains largely unknown. In our study, we found that ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer using transgenic mouse model. In addition, conditional knockout of Mettl3 in K14+ bladder cancer stem cell population leads to inhibition of bladder cancer progression. Coupled with the global transcriptome sequencing and methylated RNA immunoprecipitation sequencing results, we showed that deletion of Mettl3 leads to the suppression of tyrosine kinase endothelial (TEK) and vascular endothelial growth factor A (VEGF-A) through reduced abundance of m6A peaks on a specific region. In addition, the depletion of Mettl3 results in the decrease in both messenger RNA (mRNA) and protein levels of TEK and VEGF-A in vitro. Taken together, Mettl3-mediated m6A modification is required for the activation of TEK–VEGF-A-mediated tumor progression and angiogenesis. Our findings may provide theoretical basis for bladder cancer treatment targeting Mettl3.

scholarly journals Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xianping Che ◽  
Jiangtao Zhan ◽  
Fan Zhao ◽  
Zunhe Zhong ◽  
Mianchuan Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Akt Signaling ◽  
Bladder Cancer Cell Line ◽  
Anticancer Efficacy ◽  
T24 Cells

Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.

scholarly journals The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinan Guo ◽  
Zhixin Chen ◽  
Hongtao Jiang ◽  
Zhou Yu ◽  
Junming Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Bladder Cancer Cell ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Abstract Background Bladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression. Methods Gene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model. Results Our results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues. Conclusion Collectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.

Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo

2020 ◽  
Vol 396 (1) ◽  
pp. 112281
Author(s):  
Dayin Chen ◽  
Tingyu Chen ◽  
Yingxue Guo ◽  
Chennan Wang ◽  
Longxin Dong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Platycodin D ◽  
Lncrna Xist

scholarly journals Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis

2021 ◽  
Author(s):  
Shuilian Wu ◽  
Jialei Yang ◽  
Haotian Xu ◽  
Xin Wang ◽  
Ruirui Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Multiple Tumor ◽  
Bladder Cancer Cells

AbstractExtensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle–related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer. Graphical abstract

scholarly journals KCNMB2-AS1 Promotes Bladder Cancer Progression Through Sponging miR-374a-3p to Upregulate S100A10

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianhua Zhu ◽  
Yan Huang ◽  
Yong Zhang ◽  
Rongfu Huang ◽  
Chunmei Huang
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Crucial Role ◽  
Migration And Invasion ◽  
Non Coding Rnas ◽  
Highly Correlated ◽  
Underlying Mechanisms ◽  
Competitive Endogenous Rna

Long non-coding RNAs (lncRNAs) have been reported to play a crucial role in the pathogenesis of numerous cancers. However, the function of lncRNA KCNMB2-AS1 in bladder cancer (BC) remains unclear. In the present study, we aimed to explore the role and underlying mechanisms of KCNMB2-AS1 in bladder cancer progression. We found that lncRNA KCNMB2-AS1 was significantly upregulated both in BC tissues and cell lines, the expression level was highly correlated with pathological TNM stage. Functionally, knockdown of lncRNA KCNMB2-AS1 dramatically inhibited the proliferation, migration, and invasion and of BC cells in vitro, and suppressed tumor growth in vivo. Mechanistically, lncRNA KCNMB2-AS1 could function as a competitive endogenous RNA (ceRNA) through direct sponging miR-374a-3p, which regulated the expression of S100A10. In conclusion, our results demonstrated that lncRNA KCNMB2-AS1 can promote the progression of bladder cancer through regulation of miR-374a-3p/S100A10.

Sign in / Sign up

Export Citation Format

Share Document