Inhibitors of Epidermoid Growth Factor Receptor Suppress Cell Growth and Enhance Chemosensitivity of Nasopharyngeal Cancer Cells in vitro

Oncology ◽  
2005 ◽  
Vol 68 (4-6) ◽  
pp. 538-547 ◽  
Author(s):  
Chih-Hung Hsu ◽  
Ming Gao ◽  
Chi-Long Chen ◽  
Pei-Yen Yeh ◽  
Ann-Lii Cheng
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nasopharyngeal Cancer ◽  
Growth Factor Receptor

scholarly journals Immunity against cancer cells may promote their proliferation and metastasis

2019 ◽  
Vol 117 (1) ◽  
pp. 426-431
Author(s):  
Chih-Wei Lin ◽  
Jia Xie ◽  
Ding Zhang ◽  
Kyung Ho Han ◽  
Geramie Grande ◽  
...  
Keyword(s):  
Immune Response ◽  
Growth Factor ◽  
Cell Growth ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Point Of View ◽  
Breast Cancer Cell Growth ◽  
Agonist Antibody

Herein we present a concept in cancer where an immune response is detrimental rather than helpful. In the cancer setting, the immune system is generally considered to be helpful in curtailing the initiation and progression of tumors. In this work we show that a patient’s immune response to their tumor can, in fact, either enhance or inhibit tumor cell growth. Two closely related autoantibodies to the growth factor receptor TrkB were isolated from cancer patients’ B cells. Although highly similar in sequence, one antibody was an agonist while the other was an antagonist. The agonist antibody was shown to increase breast cancer cell growth both in vitro and in vivo, whereas the antagonist antibody inhibited growth. From a mechanistic point of view, we showed that binding of the agonist antibody to the TrkB receptor was functional in that it initiated downstream signaling identical to its natural growth factor ligand, brain-derived neurotrophic factor (BDNF). Our study shows that individual autoantibodies may play a role in cancer patients.

scholarly journals NR4A1 Ligands as Potent Inhibitors of Breast Cancer Cell and Tumor Growth

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2682
Author(s):  
Keshav Karki ◽  
Kumaravel Mohankumar ◽  
Abigail Schoeller ◽  
Gregory Martin ◽  
Rupesh Shrestha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Migration And Invasion ◽  
Binding Studies

Nuclear receptor 4A1 (NR4A1, Nur77, TR3) is more highly expressed in breast and solid tumors compared to non-tumor tissues and is a pro-oncogenic factor in solid tumor-derived cancers. NR4A1 regulates cancer cell growth, survival, migration, and invasion, and bis-indole-derived compounds (CDIMs) that bind NR4A1 act as antagonists and inhibit tumor growth. Preliminary structure-binding studies identified 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl)methane analogs as NR4A1 ligands with low KD values; we further investigated the anticancer activity of the four most active analogs (KD’s ≤ 3.1 µM) in breast cancer cells and in athymic mouse xenograft models. The treatment of MDA-MB-231 and SKBR3 breast cancer cells with the 3-bromo-5-methoxy, 3-chloro-5-trifluoromethoxy, 3-chloro-5-trifluoromethyl, and 3-bromo-5-trifluoromethoxy phenyl-substituted analogs decreased cell growth and the expression of epidermal of growth factor receptor (EGFR), hepatocyte growth factor receptor (cMET), and PD-L1 as well as inhibited mTOR phosphorylation. In addition, all four compounds inhibited tumor growth in athymic nude mice bearing MDA-MB-231 cells (orthotopic) at a dose of 1 mg/kg/d, which was not accompanied by changes in body weight. These 3,5-disubstituted analogs were the most potent CDIM/NR4A1 ligands reported and are being further developed for clinical applications.

scholarly journals Growth factor/growth factor receptor loops in autocrine growth regulation of human prostate cancer DU145 cells.

2011 ◽  
Vol 58 (3) ◽  
Author(s):  
Janusz Ligęza ◽  
Joanna Ligęza ◽  
Andrzej Klein
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Growth Regulation ◽  
Growth Factor Receptor ◽  
Human Prostate ◽  
Main Step ◽  
Autocrine Growth ◽  
Du145 Cells

Autocrine growth factors produced by epithelial cells mediate the development and proliferation of neoplastic human prostate tissue. Various approaches have been used to down-regulate neoplastic growth of prostate cancer using natural flavonoids, soluble receptors, pseudo-ligands, monoclonal antibodies and tyrosine kinase inhibitors (tyrphostins). Selected growth factor/growth factor receptor loops (mainly TGFα/EGFR and IGFs/IGFIR) have been proposed as regulators of prostate cancer cell growth. We have previously determined that blockade of IGFIR or VEGF2R signaling pathways by tyrphostin AG1024 and SU1498 inhibits autocrine growth and viability of DU145 cells in vitro. Recently, we compared the activity of AG1024 and SU1498 with the inhibiting effect of tyrphostin A23 (a selective inhibitor of EGFR). The results described in this paper confirm that DU145 cells do not produce IGFI or EGF. In contrast, DU145 cells produce a great amount of VEGF, much more than TGFα (about 60-fold), and VEGF may be the real autocrine growth factor of the investigated cells. The results indicate that the growth of DU145 may be regulated by at least three autocrine loops: TGFα/EGFR, IGFII/IGFIR and VEGF/VEGFR2. Neither AG1024 nor SU1498 affected the production of TGFα substantially, which excludes the possibility that IGFRs or VEGFR2 inhibitors arrest the growth of these cells by inhibition of synthesis and/or secretion of TGFα. The obtained data indicate that all tree investigated tyrphostins (AG1024, SU1498 and A23) inhibit signal transmission by Akt (PKB), ERK(1/2), Src and STAT in a similar manner. A comparison of the effects of the investigated tyrphostins indicates that TGFα, IGFII and VEGF stimulate cell growth by affecting the same signaling pathway. The hypothesis was confirmed by the effect of the investigated tyrphostins on activation of EGFR. All these inhibitors decreased phosphorylation of EGFR to the same extent, and after the same time of incubation with cell culture. These results strongly suggest that stimulation of EGFR kinase is the main step in the initiation of mitogen signaling in DU145 cells, regardless of the type of ligand (TGFα, IGFs or VEGF) and their specific receptors.

scholarly journals Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro.

1998 ◽  
Vol 102 (7) ◽  
pp. 1385-1392 ◽  
Author(s):  
J R Grandis ◽  
S D Drenning ◽  
A Chakraborty ◽  
M Y Zhou ◽  
Q Zeng ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Cell Growth ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals PNSA, a Novel C-Terminal Inhibitor of HSP90, Reverses Epithelial–Mesenchymal Transition and Suppresses Metastasis of Breast Cancer Cells In Vitro

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 117
Author(s):  
Aotong Zhang ◽  
Xin Qi ◽  
Fu Du ◽  
Guojian Zhang ◽  
Dehai Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation

Metastasis accounts for the vast majority of deaths in breast cancer, and novel and effective treatments to inhibit cancer metastasis remain urgently developed. The expression level of heat shock protein 90 (HSP90) in invasive breast cancer tissue is higher than in adjacent non-cancerous tissue. In the present study, we investigated the inhibitory effect of penisuloxazin A (PNSA), a novel C- terminal inhibitor of HSP90, on metastasis of breast cancer cells and related mechanism in vitro. We found that PNSA obviously affected adhesion, migration, and invasion of triple-negative breast cancer (TNBC) MDA-MB-231 cells and Trastuzumab-resistant JIMT-1 cells. Furthermore, PNSA was capable of reversing epithelial–mesenchymal transformation (EMT) of MDA-MB-231 cells with change of cell morphology. PNSA increases E-cadherin expression followed by decreasing amounts of N-cadherin, vimentin, and matrix metalloproteinases9 (MMP9) and proteolytic activity of matrix metalloproteinases2 (MMP2) and MMP9. Comparatively, the N-terminal inhibitor of HSP90 17-allyl-17-demethoxygeldanamycin (17-AAG) had no effect on EMT of MDA-MB-231 cells. PNSA was uncovered to reduce the stability of epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) proteins and thereby inhibiting their downstream signaling transductions by inhibition of HSP90. In addition, PNSA reduced the expression of programmed cell death-ligand 1 (PD-L1) to promote natural killer (NK) cells to kill breast cancer cells with a dose far less than that of cytotoxicity to NK cell itself, implying the potential of PNSA to enhance immune surveillance against metastasis in vivo. All these results indicate that PNSA is a promising anti-metastasis agent worthy of being studied in the future.

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