Abstract 1227: New small molecules targeting MYC:MAX interactions that inhibits tumor cell growth in a MYC-dependent manner

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1–mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.

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Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to domain 5 of high molecular weight kininogen

Blood ◽

10.1182/blood-2004-02-0449 ◽

2004 ◽

Vol 104 (7) ◽

pp. 2065-2072 ◽

Cited By ~ 20

Author(s):

James S. Song ◽

Irma M. Sainz ◽

Stephen C. Cosenza ◽

Irma Isordia-Salas ◽

Abdel Bior ◽

...

Keyword(s):

Molecular Weight ◽

Monoclonal Antibody ◽

Cell Growth ◽

Tumor Cell ◽

High Molecular Weight ◽

Control Group ◽

Dependent Manner ◽

Tumor Cell Growth ◽

High Molecular Weight Kininogen

Abstract We have shown that human high molecular weight kininogen is proangiogenic due to release of bradykinin. We now determined the ability of a murine monoclonal antibody to the light chain of high molecular weight kininogen, C11C1, to inhibit tumor growth compared to isotype-matched murine IgG. Monoclonal antibody C11C1 efficiently blocks binding of high molecular weight kininogen to endothelial cells in a concentration-dependent manner. The antibody significantly inhibited growth of human colon carcinoma cells in a nude mouse xenograft assay and was accompanied by a significant reduction in the mean microvascular density compared to the IgG control group. We also showed that a hybridoma producing monoclonal antibody C11C1 injected intramuscularly exhibited markedly smaller tumor mass in a syngeneic host compared to a hybridoma producing a monoclonal antibody to the high molecular weight kininogen heavy chain or to an unrelated plasma protein. In addition, tumor inhibition by purified monoclonal antibody C11C1 was not due to direct antitumor effect because there was no decrease of tumor cell growth in vitro in contrast to the in vivo inhibition. Our results indicate that monoclonal antibody C11C1 inhibits angiogenesis and human tumor cell growth in vivo and has therapeutic potential for treatment of human cancer. (Blood. 2004;104:2065-2072)

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Vitronetcin promotes cell growth and inhibits apoptotic stimuli in a human hepatoma cell line via the activation of caspases

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0032 ◽

2014 ◽

Vol 92 (5) ◽

pp. 363-368 ◽

Cited By ~ 1

Author(s):

Wei Zhu ◽

Yingzhi Liu ◽

Konghe Hu ◽

Wenxue Li ◽

Jianling Chen ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Tumor Cell ◽

Hepatoma Cell ◽

Hepatoma Cells ◽

Signaling Molecules ◽

Hepatoma Cell Line ◽

Dependent Manner ◽

Tumor Cell Growth ◽

Induced Apoptosis

This study sought to understand the effects of vitronectin (VTN) on the growth of SMMC-7721 hepatoma cells. In addition, this study examined how VTN inhibits the induction of apoptosis in SMMC-7721 cells by 3,3′-diindolylmethane (DIM), a metabolite of natural phytochemicals, and preliminarily investigated the signaling molecules involved in this process. A cell proliferation reagent was used to observe the effects of VTN on cell proliferation rates. Laser scanning confocal microscopy was performed to observe the effects of VTN on the morphology of tubulin, a component of the cytoskeleton. Flow cytometry and Western blotting assays were used to observe the inhibitory effects of VTN on DIM-induced apoptosis in SMMC-7721 cells and changes in the expression levels of the signaling molecules involved in this process. VTN promoted tumor cell growth in a concentration-dependent manner and inhibited apoptosis caused by the effects of apoptosis-inducing agents. Under in vitro experimental conditions, VTN contributed to the growth of SMMC-7721 hepatoma cells and protected them from the effects of an apoptosis-inducing agent. These findings suggest that during hepatocellular carcinogenesis, VTN may promote tumor cell growth and inhibit chemically induced apoptosis.

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Anti-Tumour Effects of High Affinity L-type Amino Acid Transporter1 Inhibitors on Human Pancreatic Adencarcinoma Cells

Journal of National Institute of Neurosciences Bangladesh ◽

10.3329/jninb.v2i2.34095 ◽

2017 ◽

Vol 2 (2) ◽

pp. 55-68

Author(s):

Rafiqul Islam ◽

Nesar Ahmed ◽

Shamima Akhter Ferdousy ◽

Mohammad Shah Jahirul Haque Chowdhury ◽

Md Tauhidul Islam Chowdhury ◽

...

Keyword(s):

Amino Acid ◽

Cell Growth ◽

Tumor Cell ◽

Growth Inhibition ◽

Life Span ◽

Pancreatic Adenocarcinoma ◽

Nude Mice ◽

Dependent Manner ◽

Tumor Cell Growth ◽

Mib 1

Background: a system L transporter L-type amino acid transporter 1 (LAT1) is upregulated to support tumor cell growth in malignant tumor. Objective: The purpose of the present study was to investigate the growth inhibition and [14C] L-leucine transport in human pancreatic adenocarcinoma cells MAIPaCa-2 and BXPC3. Methodology: This animal study was carried out in Japan. The in vitro growth inhibition study was performed by using KYT0351 and KYT0353 which inhibited the tumor cell growth in dose dependent manner and uptake of [14C] L-leucine by MIAPaCa-2 and BXPC3 cells was Na+- independent and was strongly inhibited by KYT0351 and KYT0353. The in vivo tumor growth inhibition was also carried out by intra tumor injection of KYT0351 and KYT0353 at the concentration of 2.6mM of each on both the MIAPaCa-2 and BXPC3 nude mice tumor. Result: In a subsequent survival study with the intra peritoneal injection of ascites mice model, control mice had a mean life span of 20 ± 4.30 days and 21 ± 5 days in MIAPaCa-2 and BXPC3 cells respectively, whereas the intraperitoneal injection of 10mg/kg twice daily of KYT0351 and KYT0353 group had improved survival (mean life span 28.4 ± 8.5 and 34.4 ± 9.86 days, 26 ±4.52 and 31.8 ± 7.62 days respectively in MIAPaCa-2 and BXPC3 cells). Kaplan-Meier survival data of nude mice treated with KYT0351 and KYT0353 were significant. To study the mechanism of growth inhibition we investigated the MIB-1 proliferation assay and TUNEL assay. Significantly less MIB-1 staining and more apoptotic nuclei was detected in tumors treated with KYT0351 and KYT0353 in both MIAPaCa-2 and BXPC3 cells compared with saline treated group. Conclusion: In conclusion both the KYT0351 and KYT0353 is a potent LAT1-specific inhibitor and LAT1 could be one of the molecular target in pancreatic adenocarcinoma therapy. Journal of National Institute of Neurosciences Bangladesh, 2016;2(2): 55-68

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SLMP53-1 inhibits tumor cell growth through regulation of glucose metabolism and angiogenesis in a P53-dependent manner

10.3390/ecmc2020-07400 ◽

2020 ◽

Author(s):

Juliana Calheiros ◽

Lucília Saraiva ◽

Helena Ramos ◽

Carla Carvalho ◽

Valentina Barcherini ◽

...

Keyword(s):

Cell Growth ◽

Glucose Metabolism ◽

Tumor Cell ◽

Dependent Manner ◽

Tumor Cell Growth

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Ras association domain family 1 isoform A suppresses colonic tumor cell growth through p21 WAF1 activation in a p53‐dependent manner

Journal of Gastroenterology and Hepatology ◽

10.1111/jgh.14469 ◽

2018 ◽

Vol 34 (5) ◽

pp. 890-898 ◽

Cited By ~ 2

Author(s):

Shin Ju Oh ◽

Min‐Goo Lee ◽

Jung Rock Moon ◽

Chang Kyun Lee ◽

Sung‐Gil Chi ◽

...

Keyword(s):

Cell Growth ◽

Tumor Cell ◽

Dependent Manner ◽

Tumor Cell Growth ◽

Domain Family ◽

Colonic Tumor ◽

P21 Waf1

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Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo

Molecules ◽

10.3390/molecules25204608 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4608 ◽

Cited By ~ 1

Author(s):

Xiao-Fan Huang ◽

Kai-Fu Chang ◽

Shan-Chih Lee ◽

Gwo-Tarng Sheu ◽

Chia-Yu Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Tumor Cell ◽

Dependent Manner ◽

Tumor Cell Growth ◽

Normal Cells ◽

Cedrus Atlantica ◽

Anti Cancer

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

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