scholarly journals Molecular mechanism of epidermal growth factor receptor pathway mediated adhesion and invasion of Caco-2 cell line

2005 ◽  
Vol 13 (4) ◽  
pp. 483
Author(s):  
Xiao-Jing Zhang ◽  
Liang Zhang ◽  
Yun-Peng Liu ◽  
Ke-Zuo Hou ◽  
Shu-Bao Wang
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Molecular Mechanism ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Adhesion And Invasion

scholarly journals Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1559
Author(s):  
Amena Ali ◽  
Abuzer Ali ◽  
Abu Tahir ◽  
Md. Afroz Bakht ◽  
Salahuddin ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
Growth Factor Receptor ◽  
Molecular Engineering ◽  
Curcumin Analogs ◽  
Epidermal Growth

Cancer is the world’s second leading cause of death, accounting for nearly 10 million deaths and 19.3 million new cases in 2020. Curcumin analogs are gaining popularity as anticancer agents currently. We reported herein the isolation, molecular engineering, molecular docking, antiproliferative, and anti-epidermal growth factor receptor (anti-EGFR) activities of curcumin analogs. Three curcumin analogs were prepared and docked against the epidermal growth factor receptor (EGFR), revealing efficient binding. Antiproliferative activity against 60 NCI cancer cell lines was assessed using National Cancer Institute (NCI US) protocols. The compound 3b,c demonstrated promising antiproliferative activity in single dose (at 10 µM) as well as five dose (0.01, 0.10, 1.00, 10, and 100 µM). Compound 3c inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI50) values ranging from 1.48 to 2.73 µM, and the most promising inhibition with GI50 of 1.25 µM was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI50 value of 7.29 µM. Compounds 3b,c demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound 3c had the most significant interaction with four H-bonds and three π–π stacking, and compound 3c was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program.

scholarly journals CLM3, a Multitarget Tyrosine Kinase Inhibitor With Antiangiogenic Properties, Is Active Against Primary Anaplastic Thyroid Cancer In Vitro and In Vivo

2014 ◽  
Vol 99 (4) ◽  
pp. E572-E581 ◽  
Author(s):  
Alessandro Antonelli ◽  
Guido Bocci ◽  
Poupak Fallahi ◽  
Concettina La Motta ◽  
Silvia Martina Ferrari ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Thyroid Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Growth Factor Receptor ◽  
Anaplastic Thyroid Cancer ◽  
Antiangiogenic Activity ◽  
Epidermal Growth

Context and Objective: We have studied the antitumor activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, and vascular endothelial growth factor (VEGF) receptor and with antiangiogenic activity] in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer), and in an ATC-cell line (AF). Design and Main Outcome Measures: CLM3 was tested in primary ATC cells at the concentrations of 5, 10, 30, and 50 μM; in 8305C cells, in AF cells, at 1, 5, 10, 30, 50, or 100 μM; and in AF cells in CD nu/nu mice. Results: CLM3 significantly inhibited the proliferation of 8305C and AF cells, also inducing apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < .01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose dependently (P < .001, ANOVA) and inhibited migration (P < .01) and invasion (P < .001). The AF cell line was injected sc in CD nu/nu mice, and tumor masses became detectable 15 days later. CLM3 (50 mg/kg per die) significantly inhibited tumor growth (starting 16 d after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited epidermal growth factor receptor, AKT, and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells. Conclusions: The antitumor and antiangiogenic activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.

scholarly journals Molecular Mechanism for a Role of SHP2 in Epidermal Growth Factor Receptor Signaling

2003 ◽  
Vol 23 (21) ◽  
pp. 7875-7886 ◽  
Author(s):  
Yehenew M. Agazie ◽  
Michael J. Hayman
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Molecular Mechanism ◽  
Receptor Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Tyrosine Kinase Signaling ◽  
Epidermal Growth

ABSTRACT The Src homology 2-containing phosphotyrosine phosphatase (SHP2) is primarily a positive effector of receptor tyrosine kinase signaling. However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action of SHP2 in the epidermal growth factor-induced mitogenic pathway. We demonstrate that SHP2 acts upstream of Ras and functions by increasing the half-life of activated Ras (GTP-Ras) in the cell by interfering with the process of Ras inactivation catalyzed by Ras GTPase-activating protein (RasGAP). It does so by inhibition of tyrosine phosphorylation-dependent translocation of RasGAP to the plasma membrane, to its substrate (GTP-Ras) microdomain. Inhibition is achieved through the dephosphorylation of RasGAP binding sites at the level of the plasma membrane. We have identified Tyr992 of the epidermal growth factor receptor (EGFR) to be one such site, since its mutation to Phe renders the EGFR refractory to the effect of dominant-negative SHP2. To our knowledge, this is the first report to outline the site and molecular mechanism of action of SHP2 in EGFR signaling, which may also serve as a model to describe its role in other receptor tyrosine kinase signaling pathways.

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