scholarly journals Effects of Vanadyl Complexes with Acetylacetonate Derivatives on Non-Tumor and Tumor Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5534
Author(s):  
Valentina Boscaro ◽  
Alessandro Barge ◽  
Annamaria Deagostino ◽  
Elena Ghibaudi ◽  
Enzo Laurenti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinases ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Dependent Manner ◽  
Inhibition Of Proliferation ◽  
Mitogen Activated Protein Kinases ◽  
Vanadyl Complexes ◽  
Mitogen Activated Protein

Vanadium has a good therapeutic potential, as several biological effects, but few side effects, have been demonstrated. Evidence suggests that vanadium compounds could represent a new class of non-platinum, metal antitumor agents. In the present study, we aimed to characterize the antiproliferative activities of fluorescent vanadyl complexes with acetylacetonate derivates bearing asymmetric substitutions on the β-dicarbonyl moiety on different cell lines. The effects of fluorescent vanadyl complexes on proliferation and cell cycle modulation in different cell lines were detected by ATP content using the CellTiter-Glo Luminescent Assay and flow cytometry, respectively. Western blotting was performed to assess the modulation of mitogen-activated protein kinases (MAPKs) and relevant proteins. Confocal microscopy revealed that complexes were mainly localized in the cytoplasm, with a diffuse distribution, as in podocyte or a more aggregate conformation, as in the other cell lines. The effects of complexes on cell cycle were studied by cytofluorimetry and Western blot analysis, suggesting that the inhibition of proliferation could be correlated with a block in the G2/M phase of cell cycle and an increase in cdc2 phosphorylation. Complexes modulated mitogen-activated protein kinases (MAPKs) activation in a cell-dependent manner, but MAPK modulation can only partly explain the antiproliferative activity of these complexes. All together our results demonstrate that antiproliferative effects mediated by these compounds are cell type-dependent and involve the cdc2 and MAPKs pathway.

scholarly journals Reduction of Intracellular-Reactive Oxygen Species and Diminished Mitogen-Activated Protein Kinases (MAPKs) Activation are Associated with Oral Squamous Cell Carcinoma Cell Aggressiveness

2017 ◽  
Vol 15 (2) ◽  
pp. 131-141
Author(s):  
Tanyarath UTAIPAN ◽  
Apsorn SATTAYAKHOM ◽  
Issara PRACHONGSAI ◽  
Nurdina CHARONG ◽  
Warangkana CHUNGLOK
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Protein Kinases ◽  
Cell Lines ◽  
Oxygen Species ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Oral squamous cell carcinoma (OSCC) is a serious health problem in many countries. Several drugs have been used to treat head and neck and oral cavity cancers. However, the success rate has not been impressive because of the heterogeneity of cancerous cells, resulting in differential responsiveness to chemotherapy. Two distinct phenotypes of OSCC cells, the CLS-354/WT and CLS-354/DXcells, have been used as in vitro cell models for this study. CLS-354/DXcells were more aggressive than CLS-354/WTcells, supported by the observation that CLS-354/DXcells can undergo epithelial-mesenchymal transition (EMT), grow anchorage-independently, and increase invasiveness. We investigated the preliminary redox status of these 2 cell lines, including levels of reactive oxygen species (ROS) and cellular antioxidants, using flow cytometry analysis and ABTS+ free radical scavenging assay, respectively. A 7-fold decrease in ROS level was detected in CLS-354/DXcells, comparing with CLS-354/WTcells, while antioxidant capacity was not different from that of CLS-354/WT cells. Hydrogen peroxide, a ROS modulating agent, could induce ROS levels, and caused cell death in CLS-354/WT greater than that of CLS-354/DX cells. Of note, hydrogen peroxide-induced cytotoxicity could be rescued by N-acetyl cysteine, confirming ROS-mediated cytotoxicity in both cell lines. ROS-sensitive mitogen-activated protein kinases (MAPKs) were observed using immunoblot assay. The expressions of p-JNK1/2 and p-p38 MAPK in CLS-354/DX cells were absent, while these expressions were abundantly detected in CLS-354/WTcells. This suggests that lower ROS levels, with the concomitant reduction of JNK and p38 MAPK activation in CLS-354/DX cells, are associated with cancer cell aggressiveness. These findings provide significant evidence of the resistance to ROS-modulating agents in aggressive OSCC cells.

Effects of the multikinase inhibitor regorafenib in neuroblastoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10553-10553
Author(s):  
Peter E. Zage ◽  
Divya Subramonian ◽  
Qianxing Mo ◽  
Shixia Huang
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
Cell Viability ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Therapeutic Potential ◽  
Neuroblastoma Cells ◽  
Dependent Manner ◽  
Western Blots

10553 Background: Neuroblastoma (NB) is the most common extracranial solid pediatric tumor, and children with high-risk NB have poor survival rates and need novel treatment strategies. Regorafenib, a multi-receptor tyrosine kinase (RTK) inhibitor approved for treating adult solid tumors such as advanced metastatic colorectal cancer and gastrointestinal stromal tumors, inhibits many RTKs, including PDGFR-β, VEGFR1-3, RET, c-Kit and FGFR family members. Based on the potential roles for these targets in neuroblastoma pathogenesis, we explored the therapeutic potential of Regorafenib alone and in combination with 13-cis-retinoic acid against neuroblastoma cells. Methods: We treated NB cell lines with increasing concentrations of Regorafenib and measured cell viability using MTT assays. We further measured the occupied percent confluence over time using continuous live cell imaging. We performed Western blots for caspase cleavage to measure apoptosis and flow cytometry to determine cell cycle expression. We performed Reverse Phase Protein Array (RPPA) analysis of neuroblastoma cells before and after treatment with regorafenib combined with 13- cis-retinoic acid. Results: IC50values for the tested cell lines ranged between 2.5mcM and 12.5mcM after 72 hours of exposure to Regorafenib, and decreased viability was due to a combination of apoptosis and cell cycle arrest. RPPA analysis identified alterations in multiple proteins and pathways after Regorafenib with retinoic acid treatment, including the PI3K/Akt/mTOR and Jak/Stat pathways. Phosphorylation of Erk1/2, S6, Akt, and c-Jun were decreased, while protein expression of GATA3 was increased in a dose-dependent manner. Conclusions: Regorafenib treatment results in reduced neuroblastoma cell viability and increased apoptosis via effects on several signaling pathways. Effects on intracellular signaling pathways associated with responses to the combination of regorafenib plus retinoic acid represent opportunities to develop novel combination therapies, representing potential new therapeutic strategies for children with neuroblastoma.

Advanced Glycation End Products (AGEs)-Mediated Cell Growth of Human Acute Myelogenous Leukemia Via Mitogen-Activated Protein (MAP) Kinase Pathways.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2762-2762
Author(s):  
Ju Young Kim ◽  
Hyun Ki Park ◽  
Jin Sun Yoon ◽  
Eun Shil Kim ◽  
Kwang Sung Ahn ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Myelogenous Leukemia ◽  
Dependent Manner ◽  
Glycation End Products ◽  
Mitogen Activated Protein ◽  
Acute Myelogenous ◽  
Dose Dependent

Abstract Advanced glycation end products (AGEs) are products of non-enzymatic glycation/oxidation of proteins/lipids that accumulate slowly during natural aging and at a much accelerated rate in a variety of disorders such as diabetes, renal failure, and Alzheimer’s disease. AGE modifications do not only change the physicochemical properties of the afflicted molecules, but also induce cellular signaling, activation of transcription factors and subsequent gene expression in vitro and in vivo. Most of the biologic activities associated with AGEs have been transduced by receptor for AGE (RAGE). Recently, AGEs are known to be in association with diverse cancers in terms of cellular proliferation and metastasis. However, little is known about the role of AGEs in acute myelogenous leukemia (AML). Here we examined the effects of the AGEs-RAGE interaction on the cell proliferation and intracellular signaling of AGEs in human leukemia cell lines. Expression of RAGE was observed in 8 AML cell lines examined, and up-regulated by treatment of AGE. AGE induced the proliferation of AML cell lines, HL60 and HEL, in a dose-dependent manner. Treatment with 5 μM of antisense S-ODN for RAGE did effectively inhibit cell growth of HEL cells. Exposure of HL60 and HEL with AGE induced a significant increase in the numbers of cells in S phase of cell cycle in a dose-dependent manner. AGE enhanced the expression of cell cycle regulatory proteins such as cyclin-dependent kinase (CDK) 2/4/6, cyclin D1/E/B in a dose- and a time-dependent manner. In addition, the protein levels of the cyclin-dependent kinase inhibitor (CDKI), p21 and p27, were decreased by 24 hr exposure of AGE from 10 to 200 μg/ml in HEL. Furthermore, treatment of HEL with 200 μg/ml of AGE triggered activation of mitogen-activated protein (MAP) kinases, Erk, Akt, and p38, pathways and in nuclear translocation of transcription factors NF-kB. These results indicated that AGE induced the cell growth of human AML cells, HL60 and HEL, via augmentation of cell cycle and activation of MAPK kinase pathways. Up-regulation of RAGE by exposure of AGE suggested that cellular proliferation of AML cells might be mediated in autocrine fashion.

Characterization of the Effects of Pim Kinase Inhibition on Multiple Oncogene-Driven Cell Lines

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2662-2662
Author(s):  
Stefan David Gross ◽  
John E Robinson ◽  
Shelley Allen ◽  
April Cox ◽  
Walt E DeWolf ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Line ◽  
Protein Kinases ◽  
Cell Lines ◽  
Biological Effects ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Kinase Inhibition ◽  
In Cells

Abstract We report here the biological effects of inhibiting Pim-1, -2 and -3 serine/threonine protein kinases in cells and in vivo using a novel, potent and selective small molecule inhibitor directed against these kinases. In vitro enzyme assays revealed potent inhibition of all three Pim kinase isoforms while maintaining selectivity against more than 220 other protein kinases. In cells, compound treatment produced biological effects consistent with Pim inhibition, including a reduction in BAD protein phosphorylation. Moreover, this biological activity corresponds well with the compound’s anti-proliferative and pro-apoptotic activity in the IL-3 dependent mouse pro-B cell line Ba/F3 and in factor-indpendent Ba/F3 cell lines dependent upon the expression of BCR-Abl or TEL-JAK2 for growth and survival. Importantly, compared to the BCR-Abl driven Ba/F3 cell line, this compound was equally effective at blocking the growth of an Imatinib-resistant BCR-Abl[ T315I]-driven Ba/F3 cell line. Finally, this compound possesses pharmacokinetic properties that predict the potential for in vivo activity. Therefore, we assessed the effect of Pim kinase inhibition on tumor growth in a mouse subcutaneous tumor xenograft model employing a cell line driven by the TEL-JAK2 oncogene. Results demonstrated that the compound significantly inhibited tumor growth in a dose-dependent manner. In terms of potential clinical utility, these data show that Pim kinase inhibition could be an effective therapeutic strategy for numerous hematologic malignancies including chronic and acute myelogenous leukemias, particularly in those patients that have become resistant to existing therapies such as Imatinib.

scholarly journals Anti-proliferative activities of Byrsocarpus coccineus using ovarian cancer cell lines

2020 ◽  
Author(s):  
Caroline Ukwade ◽  
Osaretin Ebuehi ◽  
Rashidat Adisa ◽  
Santos Singh ◽  
Rajesh Singh
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leaf Extract ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Inhibition Of Proliferation ◽  
Ovarian Cancer Cell Lines

Abstract Background: Ovarian cancer is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment is surgery and cytotoxic chemotherapy, but due to its cost and side effects, medicinal plants are widely used in developing countries. Byrsocarpus coccineus plant preparation, has been administered to patients traditionally in the management of tumour in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR3 and SW626 ovarian cancer cell lines. After treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic and anti-apoptotic markers. Results: Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR3 and SW626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of p53 gene, cell cycle progression, anti-apoptotic and pro-apoptotic genes. Conclusions: These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.

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