scholarly journals Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3790
Author(s):  
Gro Elise Rødland ◽  
Sissel Hauge ◽  
Grete Hasvold ◽  
Lilli T. E. Bay ◽  
Tine T. H. Raabe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Combined Treatment ◽  
Cancer Cell Lines ◽  
Variable Extent ◽  
Synergistic Induction

Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

scholarly journals COMPARATIVE IN-VITRO ANTICANCER ACTIVITY OF THANGA PARPAM (SIDDHA GOLD DRUG) IN BREAST, LIVER, PROSTATE AND LUNG CANCER CELL LINES

2021 ◽  
Vol 12 (1) ◽  
pp. 64-67
Author(s):  
Sulthan Shajahan ◽  
Arul Amuthan
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Particle Size ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cells

Thanga parpam is a gold nanoparticle used in Siddha for many chronic and challenging diseases including cancers. Clinically it shows benefit in some cancer types, but not to all types. This study was aimed to compare the in-vitro anticancer activity of Thanga parpam in various cancer cell lines. The particle size and elements were evaluated using Scanning Electron Microscope coupled with Energy Dispersive X-Ray Spectroscopy. Thanga parpam was added to breast adenocarcinoma cells, Human hepatocellular carcinoma cells, Human prostate cancer cells and Human lung adenocarcinoma epithelial cells for 24 hours. MTT assay was used to evaluate the cell viability. Graph was drawn from the % cell viability and dose required to kill 50 % cells was calculated. The gold particles are irregular disk shaped, but agglomerated to each other and not in uniform size. The particle size varies from 17.8 nm – 448 nm. About 9.3% of gold element was present in oxide and sulfide form. It showed dose dependent killing effect on all cancer cell lines. IC50% value was 0.63, 3.51, 6.65 and 11.01 µg/ml for breast, liver, prostate and lung cancer cells respectively. Thanga parpam is a potent anticancer drug to all the four cancer cells, however higher efficacy was observed in breast, liver and prostate cancer cells.

ID: 45: EVALUATION OF CELLULAR MECHANISMS BY WHICH CINOBUFOTALIN INHIBITS OVARIAN CANCER CELL LINES FUNCTION

2016 ◽  
Vol 64 (4) ◽  
pp. 950.1-950 ◽  
Author(s):  
SH Afroze ◽  
DC Zawieja ◽  
R Tobin ◽  
C Peddaboina ◽  
MK Newell-Rogers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Ovarian Cancer Cell Lines

ObjectiveCinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of the traditional Chinese medicine giant toads (Chan su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Previously we have shown that CINO inhibits the cytotrophoblast cell function. Recently other study has shown that CINO inhibits A549, a lung cancer cell function. In this study, we assessed the effect of CINO on three different ovarian cancer cell lines; SK-OV-3, CRL-1978 and CRL-11731 to confirm whether the effect of CINO is cell specific.Study DesignWe evaluated the effect of CINO on three ovarian cancer cells SK-OV-3, CRL-1978, and CRL-11731 function in vitro. Each Cell lines were treated with different concentrations of CINO (0.1, 1, 5 and 10 µM). For each cell line cell proliferation, migration and invasion were measured by using a CellTiter Assay (Promega), Cytoselect Assay (Cell Biolabs) and by using a FluoroBlock Assay (BD) respectively. Proliferating Cell Nuclear Antigen (PCNA) was also evaluated in cell lysates of CINO treated these 3 ovarian cancer cells by western blot analysis. Cell Cycle arrest and Cell viability were determined by fluorescence-activated cell sorting (FACS) analysis. We also performed Annexin V staining on CINO treated these 3 ovarian cancer cell lines by immunofluorescence to evaluate the pro-apoptotic protein expression. In addition mitochondrial membrane potential has also been measured for all these 3 ovarian cell lines after CINO treatment using MMP kit, by FACS analysis.ResultsConcentration of CINO at 0.5 µM inhibit SK-OV-3, CRL-1978, and CRL-11731 ovarian cancer cells proliferation, migration and invasion without cell death and loss of cell viability but cell viability differs for each cell line. Each cell lines differ in response to CINO doses for PCNA expression as well as Annexin V pro-apoptotic protein expression. CINO decreases mitochondrial membrane potential for SK-OV-3 but for CRL-1978 and CRL-11731 increases in response to CINO treatment.ConclusionCINO is cell specific, as each cancer cell line responds differently. These data demonstrate that the mode of action of CINO is different on these 3 types of ovarian cancer cells.

Targeting Y397 FAK scaffolding compared with FAK kinase inhibition: Efficacy and specificity for tumor cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13547-e13547 ◽  
Author(s):  
Vita Golubovskaya ◽  
Baotran Ho ◽  
Adam Stright ◽  
Maria Zajac-Kaye ◽  
Steven N. Hochwald ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Kinase Domain ◽  
Normal Cells ◽  
Atp Binding Site ◽  
Survival Signaling ◽  
Student’S T

e13547 Background: Focal Adhesion Kinase is a non-receptor kinase which is highly overexpressed and activated or autophosphorylated in many types of tumors and plays a major role in survival signaling and metastasis. Recently, our group developed a highly specific allosteric scaffolding FAK autophosphorylation inhibitor, Y15, that blocked FAK Y397 autophosphorylation, decreased cancer cell viability, and significantly decreased breast, neuroblastoma, pancreatic and glioblastoma tumor growth. In addition, Y15 was not toxic in mice. In this study, we compared side by side efficacy of Y15 with two other FAK inhibitors in clinical trials, Pfizer PF-04554878 and Glaxo GSK-2256098. Methods: MTT, clonogenicity and Western blotting assays were used to detect the effect of FAK inhibitors on different cancer and normal cells. Student’s t-test was used for statistical analysis and p<0.05 was considered significant. Results: We tested different cancer cell lines: kidney 293T, colon SW620 and LoVo; lung A549; glioblastoma U251 and U87; breast: BT474, MDA-231, MDA-361, MDA-453, MDA-468 and T47D and pancreatic PANC-1 cancer cells with different doses of Y15, PF and GSK inhibitors by MTT assay and found that Y15 was the most effective at decreasing cancer cell viability in most cancer cell lines, with higher efficacy than PF and much higher efficacy than GSK inhibitor. The same was observed for clonogenicity assay. In addition, we found that Y15 did not significantly affect viability of normal colon (CCD-112) cells, while viability of these cells with PF and GSK decreased to 54% and 57% at a 2 microM dose, respectively, from 100% in untreated cells. In addition, Y15 significantly decreased Y397-FAK, Y418-Src, phospho- Ser 473-AKT and phospho-ERK1/2, while PF had less effect and GSK only a minimal effect in four different cancer cell lines: U251, A549, 293T and Lovo at 10 microM and 100 microM doses, showing high potency of the FAK Y397 scaffolding inhibitor. Conclusions: These data show that Y15, which inhibits the Y397 site of FAK, is more potent against cancer cells and less toxic to normal cells than FAK inhibitors that target the conserved ATP-binding site in the kinase domain.

scholarly journals An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 903 ◽  
Author(s):  
Matteo Gallazzi ◽  
Marco Festa ◽  
Paola Corradino ◽  
Clementina Sansone ◽  
Adriana Albini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Olive Oil ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Olive Mill Wastewater ◽  
Lung Cancer Cells ◽  
Lung Cancer Cell ◽  
Olive Mill

Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we assessed the cancer preventive properties exerted by a purified extract of OMWW (A009) for its activity on lung cancer cell lines. Hydroxytyrosol, the most abundant polyphenol present in our A009 extracts, was used as reference molecule in the assays performed. Extracts from OMWW from two different olive oil cultivars were used. We found that the A009 extracts limit lung cancer cell proliferation in a dose and time dependent manner. These effects were associated with the induction of apoptosis. A009 extracts were effective in inhibiting adhesion capabilities on a fibronectin layer accompanied with a reduction in their ability to generate invasive sprouts in a Matrigel layer. The production of chemokine CXCL12 and CXCR4 receptor were reduced by treatment with the extracts. Also, A009 interfered with the production of proangiogenic and pro-inflammatory VEGF, CXCL8, and CCL2 (as detected by FACS analysis) in the lung cell lines. A009 extracts were able to decrease STAT3 phosphorylation in lung cancer cells. Our results show that A009 extracts reduced activities related to tumor cell behavior in lung cancer cell lines, suggesting that they could have a potential cancer preventive role.

scholarly journals FAM188B Downregulation Sensitizes Lung Cancer Cells to Anoikis via EGFR Downregulation and Inhibits Tumor Metastasis In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 247
Author(s):  
Eun-Ju Jang ◽  
Jee Young Sung ◽  
Ha-Eun Yoo ◽  
Hyonchol Jang ◽  
Jaegal Shim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Anoikis Resistance ◽  
Protein Levels

Anoikis is a type of apoptosis induced by cell detachment from the extracellular matrix (ECM), which removes mislocalized cells. Acquisition of anoikis resistance is critical for cancer cells to survive during circulation and, thus, metastasize at a secondary site. Although the sensitization of cancer cells to anoikis is a potential strategy to prevent metastasis, the mechanism underlying anoikis resistance is not well defined. Although family with sequence similarity 188 member B (FAM188B) is predicted as a new deubiquitinase (DUB) member, its biological function has not been fully studied. In this study, we demonstrated that FAM188B knockdown sensitized anoikis of lung cancer cell lines expressing WT-EGFR (A549 and H1299) or TKI-resistant EGFR mutant T790M/L858R (H1975). FAM188B knockdown using si-FAM188B inhibited the growth of all three human lung cancer cell lines cultured in both attachment and suspension conditions. FAM188B knockdown resulted in EGFR downregulation and thus decreased its activity. FAM188B knockdown decreased the activities of several oncogenic proteins downstream of EGFR that are involved in anoikis resistance, including pAkt, pSrc, and pSTAT3, with little changes to their protein levels. Intriguingly, si-FAM188B treatment increased EGFR mRNA levels but decreased its protein levels, which was reversed by treatment with the proteasomal inhibitor MG132, indicating that FAM188B regulates EGFR levels via the proteasomal pathway. In addition, cells transfected with si-FAM188B had decreased expression of FOXM1, an oncogenic transcription factor involved in cell growth and survival. Moreover, FAM188B downregulation reduced metastatic characteristics, such as cell adhesion, invasion, and migration, as well as growth in 3D culture conditions. Finally, tail vein injection of si-FAM188B-treated A549 cells resulted in a decrease in lung metastasis and an increase in mice survival in vivo. Taken together, these findings indicate that FAM188B plays an important role in anoikis resistance and metastatic characteristics by maintaining the levels of various oncogenic proteins and/or their activity, leading to tumor malignancy. Our study suggests FAM188B as a potential target for controlling tumor malignancy.

scholarly journals Chemoprevention of NCI-H322 Lung Cancer Cells Proliferation and Tumor Regression in Murine Ascites Model by Dietary Flavonoid Quercetin

2021 ◽  
Vol 12 (5) ◽  
pp. 6950-6959
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Regression ◽  
Biological Activities ◽  
Cancer Cell Lines ◽  
Prunus Cerasus ◽  
Lung Cancer Cells

Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biological activities, including anticancer, antioxidant, and anti-inflammatory properties. The present study aimed to determine the anticancer efficacy of four compounds, quercetin, daidzin, rutin, and chlorogenic acid, isolated from Prunus cerasus fruit. The antiproliferative activity of four cherry isolates was determined against five different cancer cell lines (NCI-H322, A549, THP-1, MCF-7, and PC-3) by Tetrazolium bromide assay, followed by apoptosis Cell cycle analyses, mitochondrial membrane potential, cell migration test, and in vivo Ehrlich Ascites Carcinoma studies using potent bioactive lead. The cytotoxicity profile of the four molecules demonstrated that quercetin induced significant cell growth inhibition in all cancer cell lines with paramount 79% cytotoxicity against NCI-H322 lung cancer cells (IC50 value 24μM). Incubation of NCI-H322 cells with quercetin showed a concentration-dependent increase in hypo-diploid sub G0/G1 DNA fraction, exhibited consequential changes in nuclear morphology, and caused mitochondrial transmembrane potential loss of 60.3% augmented at 30 µM. Pertaining to in vivo potency, quercetin manifested 89% tumor inhibition at 50 mg/kg body weight in EAC-bearing mice. The current studies raise the potential usefulness of quercetin in chemoprevention against lung cancer cells and support its empirical use as a promising nutraceutical agent.

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