scholarly journals Galectin-3 Stimulates Tyro3 Receptor Tyrosine Kinase and Erk Signalling, Cell Survival and Migration in Human Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Nour Al Kafri ◽  
Sassan Hafizi
Keyword(s):  
Cell Migration ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Human Cancer ◽  
Serum Starvation ◽  
Human Cancer Cell Lines ◽  
Galectin 3

The TAM (Tyro3, Axl, MerTK) subfamily of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and protein S (ProS1), are implicated in tumorigenesis and chemoresistance in various cancers. The β-galactoside binding protein galectin-3 (Gal-3), which is also implicated in oncogenesis, has previously been shown to be a ligand for MerTK. However, the selectivity of Gal-3 for the other TAM receptors, and its TAM-mediated signalling and functional properties in cancer cells, remain to be explored. The present study was aimed at determining these, including through direct comparison of Gal-3 with the two canonical TAM ligands. Exogenous Gal-3 rapidly stimulated Tyro3 receptor phosphorylation to the same extent as the Tyro3 ligand ProS1, but not Axl, in the cultured human cancer cell lines SCC-25 (express both Tyro3 and Axl) and MGH-U3 (express Tyro3 only). Gal-3 also activated intracellular Erk and Akt kinases in both cell lines and furthermore protected cells from acute apoptosis induced by staurosporine but not from serum-starvation induced apoptosis. In addition, Gal-3 significantly stimulated cancer cell migration rate in the presence of the Axl blocker BGB324. Therefore, these results have shown Gal-3 to be a novel agonist for Tyro3 RTK, activating a Tyro3-Erk signalling axis, as well as Akt signalling, in cancer cells that promotes cell survival, cell cycle progression and cell migration. These data therefore reveal a novel mechanism of Tyro3 RTK activation through the action of Gal-3 that contrasts with those of the known TAM ligands Gas6 and ProS1.

scholarly journals Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1843 ◽  
Author(s):  
Nour Al Kafri ◽  
Sassan Hafizi
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Human Cancer ◽  
Protein S ◽  
Serum Starvation ◽  
Secondary Resistance ◽  
Human Cancer Cell Lines ◽  
Ligand Selectivity ◽  
Kinase Phosphorylation

The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including its ligand selectivity and signalling in cancer cells. Tyro3 showed widespread protein and mRNA expression in a variety of human cancer cell lines. In SCC-25 head and neck cancer cells expressing both Tyro3 and Axl, Western blotting showed that both natural TAM ligands ProS1 and Gas6 rapidly stimulated Tyro3 and Erk kinase phosphorylation, with ProS1 eliciting a greater effect. In contrast, Gas6 was the sole stimulator of Axl and Akt kinase phosphorylation. In MGH-U3 bladder cancer cells, which express Tyro3 alone, ProS1 was again the stronger stimulator of Tyro3 and Erk stimulation but additionally stimulated Akt phosphorylation. Conditioned medium from ProS1-secreting 786-0 kidney cancer cells replicated the kinase activation effects of recombinant ProS1 in SCC-25 cells, with specificity confirmed by ProS1 ligand traps and warfarin. In addition, ProS1 protected cancer cells from acute apoptosis induced by staurosporine, as well as additionally, long-term serum starvation-induced apoptosis in MGH-U3 cells (Tyro3 only), which reflects its additional coupling to Akt signalling in these cells. In conclusion, we have shown that ProS1 is a tumour-derived functional ligand for Tyro3 that supports cancer cell survival. Furthermore, the ProS1-Tyro3 interaction is primarily coupled to Erk signalling although it displays signalling diversity dependent upon its representative expression as a TAM receptor in tumour cells.

scholarly journals Triterpenoidal and Phenolic Compounds Isolated from the Aerial Parts of Helicteres hirsuta and their Cytotoxicity on Several Cancer Cell Lines

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400
Author(s):  
Triet Thanh Nguyen ◽  
Nadine Kretschmer ◽  
Eva-Maria Pferschy-Wenzig ◽  
Olaf Kunert ◽  
Rudolf Bauer
Keyword(s):  
Phenolic Compounds ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Moderate Activity ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Helicteres Isora

Helicteres L. is one of the genera of the Sterculiaceae family with several remarkable activities. Previous studies revealed that terpenoids, flavonoids, and lignans are the dominant constituents of Helicteres species. However, information about this genus is scarce and unsystematic. Most of the phytochemical and pharmacological investigations have been mainly reported on Helicteres angustifolia and Helicteres isora, which are commonly used in China and Indonesia, respectively. In the present study, two terpenoids: 3β- O-acetylbetulinic acid (1) and simiarenol (2) together with three phenolic compounds: 4,4'-sulfinylbis(2-( tert-butyl)-5-methylphenol) (3), 7- O-methylisoscutellarein (4), 7,4'-di- O-methylisoscutellarein (5), and a mixture of stigmasterol and β-sitosterol were isolated and structurally elucidated from the aerial parts of Helicteres hirsuta Lour. Compounds 1-5 were tested for cytotoxicity on four human cancer cell lines: leukemia CCRF-CEM, breast MDA-MB-231, colon HCT116 and glioblastoma U251 cancer cells. Among them, compounds 1 and 3 showed moderate activity on CCRF-CEM and HCT116 cancer cells with IC50 values ranging from 14.6 to 31.5 μM (P < 0.05). This is the first time these compounds have been reported from this plant. To the best of our knowledge, compound 3 is novel in nature although it has been chemically synthesized before, and compounds 1, 2, and 4 are new to this plant family (Sterculiaceae).

An IMDAF approach to annellated 1,4:5,8-diepoxynaphthalenes and their metathesis reaction leading to novel scaffolds displaying an antiproliferative activity toward cancer cells

2021 ◽  
Author(s):  
Elizaveta A. Kvyatkovskaya ◽  
Kseniya K. Borisova ◽  
Polina P. Epifanova ◽  
Aleksey A. Senin ◽  
Victor N. Khrustalev ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Metathesis Reaction ◽  
Human Cancer Cell Lines ◽  
Antiproliferative Agent

A 3,5a-epoxyfuro[2,3,4-de]isoquinoline scaffold, the product of ROCM of 1,4:5,8-diepoxynaphthalenes, is a promising antiproliferative agent toward breast and prostate human cancer cell lines.

scholarly journals In vitro photodynamic treatment of cancer cells induced by aza-BODIPYs

2020 ◽  
Vol 19 (6) ◽  
pp. 790-799
Author(s):  
Miryam Chiara Malacarne ◽  
Stefano Banfi ◽  
Enrico Caruso
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Iodine Atom ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Photodynamic Treatment ◽  
Human Cancer Cell Lines

Two new aza-BODIPY photosensitizers featuring an iodine atom on each pyrrolic unit of their structure, were synthesized in fairly good yields and tested in vitro on two human cancer cell lines to assess their photodynamic efficacy.

scholarly journals Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells

2021 ◽  
Author(s):  
Yaakov Elisha Stern ◽  
Stephanie Duhamel ◽  
Abdulhameed Al-Ghabkari ◽  
Anie Monast ◽  
Benoit Fiset ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Human Cancer ◽  
Transmembrane Protein ◽  
Cancer Cell Lines ◽  
Her Family

Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting in increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal crosstalk with several members of the human EGFR (HER) family of RTKs when amplified in cancer cells. We show that Met signaling converges on HER3 tyrosine phosphorylation across a panel of seven MET-amplified cancer cell lines and that HER3 is required for cancer cell expansion and oncogenic capacity in-vitro and in-vivo. Gene expression analysis of HER3-depleted cells identified MPZL3, encoding a single-pass transmembrane protein, as a HER3-dependent effector in multiple MET-amplified cancer cell lines. MPZL3 interacts with HER3 and MPZL3 loss phenocopies HER3 loss in MET-amplified cells, while MPZL3 overexpression rescues proliferation upon HER3 depletion. Together, these data support an oncogenic role for a HER3-MPZL3 axis in MET-amplified cancers.

Novel Artemisinin-Derived Dimers: Synthesis and Evaluation of Anti-cancer Activities

2016 ◽  
Vol 14 (1) ◽  
pp. 102-111 ◽  
Author(s):  
Vu Tuan Kien ◽  
Le Huy Binh ◽  
Phan Hai Phong ◽  
Doan Thi Hien ◽  
Nguyen Thi Thuy My ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Anticancer Compounds ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
Mcf 7

In continuation of our study on anticancer compounds, a series of novel artemisinin dimers have been synthesized and evaluated for their cytotoxic effects against three human cancer cell lines, including HepG2 (liver cancer), MCF-7(breast cancer) and HL-60 (leukemia cancer). The assay results showed that most of the compounds displayed inhibitory effects against all three human cancer cell lines tested, and seemed to be more cytotoxic toward the blood cancer cells (HL-60) than liver (HepG2), and breast (MCF-7) cancer cells. Among the synthesized artemisinin dimers, the compound 10d with a double bond bridge exhibited the most potent cytotoxicity with IC50 values of 5.08, 4.82 and 1.32 µg/mL against the HepG2, MCF-7, and HL-60 cell lines, respectively.

Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel

Metallomics ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 1132-1141 ◽  
Author(s):  
Ana Podolski-Renić ◽  
Szilvia Bősze ◽  
Jelena Dinić ◽  
László Kocsis ◽  
Ferenc Hudecz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Oxidative Agents

Epimeric ferrocene–quinidine hybrids with triazolyl-chalcone linkers act as pro-oxidative agents and autophagy modulators in paclitaxel resistant cancer cells.

scholarly journals Beef conjugated linoleic acid isomers reduce human cancer cell growth even when associated with other beef fatty acids

2006 ◽  
Vol 95 (2) ◽  
pp. 346-352 ◽  
Author(s):  
Anne De La Torre ◽  
Eric Debiton ◽  
Pierre Juanéda ◽  
Denys Durand ◽  
Jean-Michel Chardigny ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Cancer Cells ◽  
Conjugated Linoleic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Antiproliferative Effects ◽  
Human Cancer Cell Lines

Although many data are available concerning anticarcinogenic effects of industrial conjugated linoleic acid (CLA), few studies have reported the antitumour properties of CLA mixtures originating from ruminant products. The aim of the present study was to investigate thein vitroantiproliferative effects of beef CLA mixtures on breast, lung, colon, melanoma and ovarian human cancer cell lines. For this purpose, four fatty acid (FA) extracts prepared from beef lipid and varying in their CLA composition, their corresponding purified CLA-enriched fractions, and mixtures of pure synthetic CLA, the composition of which reproduced that of the four selected beef samples, were tested on cancer cell lines. Cancer cells were exposed for 48h to medium containing 100μm-FA and their proliferation was determined by quantifying cellular DNA content (Hoechst 33342 dye). Compared with cells incubated without FA, the number of cancer cells was reduced from 25 to 67% (P<0·0001) following FA treatment. Antiproliferative effects of CLA mixtures varied in magnitude according to the source of FA, the CLA composition and the cell lines. CLA mixtures naturally present in beef inhibited the proliferation of human cancer cell lines, a high content incis-transisomers allowing the most important antiproliferative effect. Beef total FA exhibited a greater growth-inhibitory activity than their corresponding CLA-enriched fractions. These results suggested that either beef FA other than beef CLA could possess antiproliferative properties and/or the existence of complementary effects of non-conjugated FA and CLA, which could favour the antiproliferative properties of beef total FA.

5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: design, synthesis and cytotoxicity against cancer cells

2016 ◽  
Vol 14 (21) ◽  
pp. 4829-4841 ◽  
Author(s):  
Sajita Shah ◽  
Chaemin Lee ◽  
Hyukjae Choi ◽  
Jaya Gautam ◽  
Hyeonjin Jang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Hybrid Compounds

Synthesis of a series of hybrid compounds of pyridinol and sunitinib and their cytotoxicity against human cancer cell lines and improved safety windows are described.

Induction of tenascin in cancer cells by interactions with embryonic mesenchyme mediated by a diffusible factor

1993 ◽  
Vol 104 (2) ◽  
pp. 289-296 ◽  
Author(s):  
N. Hiraiwa ◽  
H. Kida ◽  
T. Sakakura ◽  
M. Kusakabe
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Culture Media ◽  
Human Cancer ◽  
Early Stage ◽  
Cancer Cell Lines ◽  
Epithelial Cancer ◽  
Human Cancer Cell Lines

Human cancer cell lines A431 and MCF7, which do not produce tenascin (TN) in vitro, were found to produce TN when injected into nude mice or co-cultured with the embryonic mesenchyme. The TN expression in the developing A431 solid tumor was demonstrated by immunohistochemistry and by in situ hybridization. Human TN was detected in culture media by western blot analysis using human specific monoclonal antibody (RCB-1). During tumorigenesis, in the early stage, mouse TN was actively induced and deposited in the peri- and intertumor spaces surrounding the developing tumor. Two days later, TN derived from human epithelial cancer cells was induced and mainly deposited in the intertumor basement membrane. After this stage, tumor cells were actively producing TN. On the other hand, TN induction in non TN-producing cells, such as A431 and MCF7 cell lines, was also observed in vitro. Although cell lines such as NIH-3T3, phi 2, STO, 2H6, 3E5 and CMT315, had no effect on the TN induction, primary cultured embryonic mesenchyme effectively stimulated the TN expression in the cancer cell lines. This mesenchymal effect decreased with age and was entirely lost postnatally. Furthermore, conditioned media from these embryonic mesenchymes could reproduce the same effects on TN induction as observed in the co-culture study. In conclusion, these findings suggest that TN induction in epithelial cancer cells may depend on interactions with the surrounding environment, that these interactions may be mediated by a soluble factor(s) derived from the surrounding mesenchyme and that the TN induction observed in the tumorigenesis may reflect histogenesis during the embryonic period.

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