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

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

scholarly journals miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

2018 ◽  
Vol 51 (4) ◽  
pp. 1969-1981 ◽  
Author(s):  
Xiangyu Zhu ◽  
Si-ping Ma ◽  
Dongxiang Yang ◽  
Yanlong Liu ◽  
Yong-peng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Nude Mice ◽  
Colony Formation ◽  
Tumor Cell Growth ◽  
Rt Pcr ◽  
Tumor Tissues

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.

scholarly journals p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression

2008 ◽  
Vol 183 (4) ◽  
pp. 737-749 ◽  
Author(s):  
Edwin Soto ◽  
Masahiro Yanagisawa ◽  
Laura A. Marlow ◽  
John A. Copland ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Tumor Cell Growth ◽  
P120 Catenin ◽  
Opposing Effects ◽  
E Cadherin

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.

Synthesis, characterization and tumor cell growth inhibition of new trans platinum complexes with phosphane derivatives

Polyhedron ◽  
2011 ◽  
Vol 30 (10) ◽  
pp. 1646-1650 ◽  
Author(s):  
A.G. Quiroga ◽  
F.J. Ramos-Lima ◽  
A. Alvarez-Valdés ◽  
M. Font-Bardía ◽  
A. Bergamo ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Platinum Complexes ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition

Tumor Cell Growth Inhibition by Liposome-Encapsulated Aromatic Polyamidines

1990 ◽  
Vol 79 (8) ◽  
pp. 672-677 ◽  
Author(s):  
C. Nastruzzi ◽  
R. Gambari ◽  
E. Menegatti ◽  
P. Walde ◽  
P.L. Luisi
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition

scholarly journals In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts

2021 ◽  
Vol 18 (18) ◽  
pp. 9917
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán-Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Endophytic Fungi ◽  
Tumor Cell Growth ◽  
Cell Growth Inhibition ◽  
Antitumor Effects ◽  
Ht 29 ◽  
Mcf 7

Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.

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

2016 ◽  
Author(s):  
Alina Castell ◽  
Karin Ridderstråle ◽  
Qinzi Yan ◽  
Fan Zhang ◽  
Per Hydbring ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Small Molecules ◽  
Dependent Manner ◽  
Tumor Cell Growth

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

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2065-2072 ◽  
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)

scholarly journals Analysis of wild-type and mutant p21WAF-1 gene activities.

1996 ◽  
Vol 16 (4) ◽  
pp. 1786-1793 ◽  
Author(s):  
J Lin ◽  
C Reichner ◽  
X Wu ◽  
A J Levine
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Tumor Cell ◽  
Cyclin D1 ◽  
Cyclin E ◽  
Growth Suppression ◽  
Nuclear Antigen ◽  
Tumor Cell Growth ◽  
Amino Acid Residues ◽  
Wild Type

The p21WAF-1 gene is positively regulated by the wild-type p53 protein. p21WAF-1 has been shown to interact with several cyclin-dependent kinase complexes and block the activity of G1 cyclin-dependent kinases (cdks). Mutational analysis with the p21WAF-1 gene localized a site, at amino acid residues 21 and 24 in the amino terminus of the protein, for p21WAF-1 binding to cyclins D and E. This region of the protein is conserved (residues 21 to 26) in other p21WAF-1 family members, p27kip-1 and p57kip-2. The same p21WAF-121,24 mutant also fails to bind to cyclin D1-cdk 4 or cyclin E-cdk 2 complexes in vitro, suggesting that amino acid residues 21 and 24 are important for p21WAF-1-cdk-cyclin trimeric complex interactions. The p21WAF-1 wild-type protein will suppress tumor cell growth in culture while p21WAF-1 mutant proteins with defects in residues 21 and 24 fail to suppress tumor cell growth. The overexpression of cyclin D or E in these cells will partially overcome the growth suppression of wild-type p21WAF-1 protein in cells. These results provide evidence that p21WAF-1 acts through cyclin D1-cdk4 and cyclin E-cdk2 complexes in vivo to induce the growth suppression. The p21WAF-1 binding sites for cyclins (residues 21 to 26), cdk2 (residues 49 to 71), and proliferating-cell nuclear antigen (residues 124 to 164) have all been mapped to discrete sites on the protein.

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