scholarly journals Adenosine Suppresses Cholangiocarcinoma Cell Growth and Invasion in Equilibrative Nucleoside Transporters-Dependent Pathway

2020 ◽  
Vol 21 (3) ◽  
pp. 814 ◽  
Author(s):  
Kornkamon Lertsuwan ◽  
Supathra Phoaubon ◽  
Nathapol Tasnawijitwong ◽  
Jomnarong Lertsuwan
Keyword(s):  
Cell Growth ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Adenosine Kinase ◽  
Nucleoside Transporters ◽  
Cancer Cell Growth ◽  
Equilibrative Nucleoside Transporters ◽  
Cholangiocarcinoma Cell ◽  
Amp Activated Protein Kinase ◽  
Dependent Pathway

Cholangiocarcinoma (CCA) is a lethal disease with increasing incidence worldwide. Previous study showed that CCA was sensitive to adenosine. Thereby, molecular mechanisms of CCA inhibition by adenosine were examined in this study. Our results showed that adenosine inhibited CCA cells via an uptake of adenosine through equilibrative nucleoside transporters (ENTs), instead of activation of adenosine receptors. The inhibition of ENTs by NBTI caused the inhibitory effect of adenosine to subside, while adenosine receptor antagonists, caffeine and CGS-15943, failed to do so. Intracellular adenosine level was increased after adenosine treatment. Also, a conversion of adenosine to AMP by adenosine kinase is required in this inhibition. On the other hand, inosine, which is a metabolic product of adenosine has very little inhibitory effect on CCA cells. This indicates that a conversion of adenosine to inosine may reduce adenosine inhibitory effect. Furthermore, there was no specific correlation between level of proinflammatory proteins and CCA responses to adenosine. A metabolic stable analog of adenosine, 2Cl-adenosine, exerted higher inhibition on CCA cell growth. The disturbance in intracellular AMP level also led to an activation of 5′ AMP-activated protein kinase (AMPK). Accordingly, we proposed a novel adenosine-mediated cancer cell growth and invasion suppression via a receptor-independent mechanism in CCA.

scholarly journals LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591984373 ◽  
Author(s):  
Shuren Wang ◽  
Kai Ma ◽  
Cuiqi Zhou ◽  
Yu Wang ◽  
Guanghui Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Growth

Wnt/β-catenin and Hippo pathways play essential roles in the tumorigenesis and development of colorectal cancer. We found that Celastrol, isolated from Tripterygium wilfordii plant, exerted a significant inhibitory effect on colorectal cancer cell growth in vitro and in vivo, and further unraveled the molecular mechanisms. Celastrol induced β-catenin degradation through phosphorylation of Yes-associated protein (YAP), a major downstream effector of Hippo pathway, and also Celastrol-induced β-catenin degradation was dependent on liver kinase B1 (LKB1). Celastrol increased the transcriptional activation of LKB1, partially through the heat shock factor 1 (HSF1). Moreover, LKB1 activated AMP-activated protein kinase α (AMPKα) and further phosphorylated YAP, which eventually promoted the degradation of β-catenin. In addition, LKB1 deficiency promoted colorectal cancer cell growth and attenuated the inhibitory effect of Celastrol on colorectal cancer growth both in vitro and in vivo. Taken together, Celastrol inhibited colorectal cancer cell growth by promoting β-catenin degradation via the HSF1–LKB1–AMPKα–YAP pathway. These results suggested that Celastrol may potentially serve as a future drug for colorectal cancer treatment.

scholarly journals In Search of the Molecular Mechanisms Mediating the Inhibitory Effect of the GnRH Antagonist Degarelix on Human Prostate Cell Growth

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120670 ◽  
Author(s):  
Monica Sakai ◽  
Daniel B. Martinez-Arguelles ◽  
Nathan H. Patterson ◽  
Pierre Chaurand ◽  
Vassilios Papadopoulos
Keyword(s):  
Cell Growth ◽  
Molecular Mechanisms ◽  
Gnrh Antagonist ◽  
Inhibitory Effect ◽  
Human Prostate ◽  
Prostate Cell

7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism

2018 ◽  
Vol 40 (6) ◽  
pp. 791-804
Author(s):  
Praveen Pandey ◽  
Deepika Singh ◽  
Mohammad Hasanain ◽  
Raghib Ashraf ◽  
Mayank Maheshwari ◽  
...  
Keyword(s):  
Cell Growth ◽  
Anticancer Activity ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cancer Cell Growth ◽  
Apoptotic Pathway ◽  
Syngeneic Mouse Model ◽  
Sphaeranthus Indicus

Abstract Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anticancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant, which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in this study. Consistent with in vitro data, 7-HF caused substantial regression of tumour volume in a syngeneic mouse model of colon cancer. The molecule triggered extrinsic apoptotic pathway, which was evident as upregulation of DR4 and DR5 expression as well as induction of their downstream effector molecules (FADD, Caspase-8). Concurrent activation of intrinsic pathway was demonstrated with loss of ΔΨm to release pro-apoptotic cytochrome c from mitochondria and activation of downstream caspase cascades (Caspase -9, -3). Loss of p53 resulted in decreased sensitivity of cells towards pro-apoptotic effect of 7-HF with increased number of viable cells indicating p53-dependent arrest of cancer cell growth. This notion was further supported with 7-HF-mediated elevation of endogenous p53 level, decreased expression of MDM2 and transcriptional upregulation of p53 target genes in apoptotic pathway. However, 7-HF was equally effective in preventing progression of HCT116 p53+/+ and p53−/− cell derived xenografts in nude mice, which suggests that differences in p53 status may not influence its in vivo efficacy. Taken together, our results support 7-HF as a potential chemotherapeutic agent and provided a new mechanistic insight into its anticancer activity.

Inhibition of gastric cancer cell growth by arginine: Molecular mechanisms of action

2009 ◽  
Vol 28 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Shayanthan Nanthakumaran ◽  
Iain Brown ◽  
Steven D. Heys ◽  
Andrew C. Schofield
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cell ◽  
Mechanisms Of Action ◽  
Cancer Cell Growth

MEK inhibitor enhances the inhibitory effect of imatinib on pancreatic cancer cell growth

2008 ◽  
Vol 264 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Yuichi Takayama ◽  
Toshio Kokuryo ◽  
Yukihiro Yokoyama ◽  
Masato Nagino ◽  
Yuji Nimura ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Mek Inhibitor ◽  
Inhibitory Effect ◽  
Cancer Cell Growth
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