scholarly journals Evaluation of anticancer and antimicrobial activities of the Polygonum maritimum ethanol extract

2018 ◽  
Vol 70 (4) ◽  
pp. 665-673 ◽  
Author(s):  
Marina Jovanovic ◽  
Tatjana Srdic-Rajic ◽  
Emilija Svircev ◽  
Nebojsa Jasnic ◽  
Biljana Nikolic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Herbal Remedy ◽  
Antimicrobial Properties ◽  
Epigallocatechin Gallate ◽  
Ethanol Extract ◽  
Antimicrobial Activities ◽  
Cell Cycle Distribution ◽  
M Cell ◽  
Ic50 Values

Polygonum maritimum is a traditional herbal remedy that produces abundant flavonoid secondary metabolites. The ethanol extract of P. maritimum aerial parts (POM) was chemically characterized and tested for antimicrobial properties and cytotoxicity. Results of LC-MS/MS analysis showed high contents of gallic acid, epigallocatechin gallate and catechin, and significant amounts of quercetin-3-O-galactoside and quercetin-3-O-glucoside. Evaluation of the antifungal properties revealed that POM induced notable growth inhibition of Alternaria alternata (34.3%), Penicillium spp. (30.6%), Fusarium semitectum (20.2%) and Aspergillus spp. (19.6%). Evaluation of cytotoxicity against human hepatoma HepG2 cells included monitoring the effects of both POM alone and its combination with cytostatic doxorubicin (Dox). Cell viability, apoptosis and cell cycle distribution and the expression of antioxidant enzymes (superoxide-dismutases SOD1 and SOD2 and catalase) were determined. A dose-dependent decrease in cell viability was detected, but a remarkably stronger effect was obtained when POM and Dox were applied in combination as compared to individual treatments. IC50 values were determined to be 393 ?g/mL (POM) and 2.24 ?g/mL (Dox) in combination, but 1153 ?g/mL (POM) and 12.56 ?g/mL (Dox) in a single treatment. The value of the Loewe index, determined for IC50, was notably lower than 1 (LI=0.51), clearly indicating synergism of POM and Dox. Additionally, POM and POM +Dox induced early/late apoptosis and G2/M cell cycle arrest. Furthermore, POM increased, while Dox decreased the expression levels of SODs and catalase. The obtained results encourage further examination of the potential use of POM in modern phytotherapy.

scholarly journals Palbociclib (PD-0332991), a Potent Selective CDK4/6 Inhibitor, Overcomes Therapy-Resistant and Sensitizes Diffuse Large B-Cell Lymphoma Pre-Clinical Models to Chemo-Reagents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3997-3997
Author(s):  
Juan J Gu ◽  
Qunling Zhang ◽  
Cory Mavis ◽  
Myron S. Czuczman ◽  
Francisco J. Hernandez-Ilizaliturri
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Board ◽  
Cell Cycle Distribution ◽  
Large B Cell Lymphoma ◽  
Ic50 Values ◽  
Clinical Models

Abstract Background: Results from the Collaborative trial in relapsed aggressive lymphoma (CORAL) study highlighted the poor clinical outcome of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients previously treated with rituximab-based therapy. To better understand the molecular mechanisms underlining the acquired resistance to rituximab, we generated and characterized several rituximab-resistant DLBCL cell lines (RRCLs). We found that RRCL exhibited a unique cell cycle distribution (accumulation in S-phase) and an increase in cyclin D Kinase-4 (CDk4) mRNA/protein levels. In our current work, we evaluated Palbociclib, a novel orally bioavailable CDK4/6 inhibitor recently approved by the Food and Drug Administration for the treatment of breast cancer in rituximab-sensitive and -resistant lymphoma pre-clinical models. Methods: A panel of rituximab-sensitive cell lines (RSCL) or RRCL were exposed to escalating dosages of PD0332991 (0-80µM) for 24-72 hrs. Changes in cell viability and cell cycle distribution were evaluated using the Presto Blue assay and flow cytometry respectively. IC50 values were calculated using the GraphPad Prism6 software. Subsequently RSCL or RRCL were exposed to PD0332991 or vehicle control and doxorubicin (0.5, 1, 2µM), dexamethasone (1µM), ibrutinib (1µM), bortezomib (10-20nM) or carfilzomib (10nM) for 48 hours. Changes in cell viability were determined by the Presto Blue assay. Coefficient of synergy was calculated using the CalcuSyn software. Results: Palbociclib induced dose- and time-dependent decrease in cell viability in both RSCL and RRCL. Of interest, palbociclib was more potent in RRCL than RSCL. The IC50 values were lower in RRCL Raji-4RH and RL-4RH (12.12µM and 13.43µM) than in RSCL Raji and RL cells (14.7µM and 19.99µM). In vitro exposure of lymphoma cells to palbociclib resulted in G1 cell cycle arrested and it was more evident in RRCL than in RSCL. Synergistic activity was observed by combining palbociclib with doxorubicin, dexamethasone and proteasome inhibitors (bortezomib and carfilzomib) in vitro. Our data suggests that, palbociclib is active against in rituximab-sensitive or resistant pre-clinical models. In addition, CDK4/6 inhibition resulted in synergistic effects with several chemotherapeutic agents. A better understanding in the molecular events triggered by palbociclib is necessary to better develop optimal combination strategies using this novel agent in future clinical trials. (Research, in part, supported by a NIH grant R01 CA136907-01A1 awarded to Roswell Park Cancer Institute and The Eugene and Connie Corasanti Lymphoma Research Fund). Disclosures Czuczman: Celgene: Employment; MorphoSys: Consultancy; Immunogen: Other: Advisory board; Boehringer-Ingelheim: Other: Advisory Board.

Anlotinib Inhibits Cell Proliferation, Migration and Invasion via Suppression of c-met Pathway and Activation of ERK1/2 Pathway in H446 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiali Tang ◽  
Ying Zheng ◽  
Demin Jiao ◽  
Jun Chen ◽  
Xibang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
M Cell ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
And Migration

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

High Glucose Affects the Cytotoxic Potential of Rapamycin, Metformin and Hydrogen Peroxide in Cultured Human Mesenchymal Stem Cells

2019 ◽  
Vol 19 (9) ◽  
pp. 688-698 ◽  
Author(s):  
Azam Roohi ◽  
Mahin Nikougoftar ◽  
Hamed Montazeri ◽  
Shadisadat Navabi ◽  
Fazel Shokri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
High Glucose ◽  
Cell Cycle Distribution ◽  
Efficient Treatment ◽  
Chronic Hyperglycemia ◽  
Placental Mesenchymal Stem Cells

Background: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. Methods: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. Results: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. Conclusion: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.

scholarly journals Advantages of Tyrosine Kinase Anti-Angiogenic Cediranib over Bevacizumab: Cell Cycle Abrogation and Synergy with Chemotherapy

2021 ◽  
Vol 14 (7) ◽  
pp. 682
Author(s):  
Jianling Bi ◽  
Garima Dixit ◽  
Yuping Zhang ◽  
Eric J. Devor ◽  
Haley A. Losh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Endometrial Cancer ◽  
Tyrosine Kinase ◽  
Cell Viability ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Cell Cycle Checkpoint ◽  
Mitotic Catastrophe ◽  
M Cell

Angiogenesis plays a crucial role in tumor development and metastasis. Both bevacizumab and cediranib have demonstrated activity as single anti-angiogenic agents in endometrial cancer, though subsequent studies of bevacizumab combined with chemotherapy failed to improve outcomes compared to chemotherapy alone. Our objective was to compare the efficacy of cediranib and bevacizumab in endometrial cancer models. The cellular effects of bevacizumab and cediranib were examined in endometrial cancer cell lines using extracellular signal-related kinase (ERK) phosphorylation, ligand shedding, cell viability, and cell cycle progression as readouts. Cellular viability was also tested in eight patient-derived organoid models of endometrial cancer. Finally, we performed a phosphoproteomic array of 875 phosphoproteins to define the signaling changes related to bevacizumab versus cediranib. Cediranib but not bevacizumab blocked ligand-mediated ERK activation in endometrial cancer cells. In both cell lines and patient-derived organoids, neither bevacizumab nor cediranib alone had a notable effect on cell viability. Cediranib but not bevacizumab promoted marked cell death when combined with chemotherapy. Cell cycle analysis demonstrated an accumulation in mitosis after treatment with cediranib + chemotherapy, consistent with the abrogation of the G2/M checkpoint and subsequent mitotic catastrophe. Molecular analysis of key controllers of the G2/M cell cycle checkpoint confirmed its abrogation. Phosphoproteomic analysis revealed that bevacizumab and cediranib had both similar and unique effects on cell signaling that underlie their shared versus individual actions as anti-angiogenic agents. An anti-angiogenic tyrosine kinase inhibitor such as cediranib has the potential to be superior to bevacizumab in combination with chemotherapy.

scholarly journals COXIBs and 2,5-dimethylcelecoxib counteract the hyperactivated Wnt/β-catenin pathway and COX-2/PGE2/EP4 signaling in glioblastoma cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aleksandra Majchrzak-Celińska ◽  
Julia O. Misiorek ◽  
Nastassia Kruhlenia ◽  
Lukasz Przybyl ◽  
Robert Kleszcz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Methylation Status ◽  
Receptor Expression ◽  
Cell Cycle Distribution ◽  
Ep4 Receptor ◽  
Cox 2 ◽  
The Impact

Abstract Background Glioblastoma (GBM) is the deadliest and the most common primary brain tumor in adults. The invasiveness and proliferation of GBM cells can be decreased through the inhibition of Wnt/β-catenin pathway. In this regard, celecoxib is a promising agent, but other COXIBs and 2,5-dimethylcelecoxib (2,5-DMC) await elucidation. Thus, the aim of this study was to analyze the impact of celecoxib, 2,5-DMC, etori-, rofe-, and valdecoxib on GBM cell viability and the activity of Wnt/β-catenin pathway. In addition, the combination of the compounds with temozolomide (TMZ) was also evaluated. Cell cycle distribution and apoptosis, MGMT methylation level, COX-2 and PGE2 EP4 protein levels were also determined in order to better understand the molecular mechanisms exerted by these compounds and to find out which of them can serve best in GBM therapy. Methods Celecoxib, 2,5-DMC, etori-, rofe- and valdecoxib were evaluated using three commercially available and two patient-derived GBM cell lines. Cell viability was analyzed using MTT assay, whereas alterations in MGMT methylation level were determined using MS-HRM method. The impact of COXIBs, in the presence and absence of TMZ, on Wnt pathway was measured on the basis of the expression of β-catenin target genes. Cell cycle distribution and apoptosis analysis were performed using flow cytometry. COX-2 and PGE2 EP4 receptor expression were evaluated using Western blot analysis. Results Wnt/β-catenin pathway was attenuated by COXIBs and 2,5-DMC irrespective of the COX-2 expression profile of the treated cells, their MGMT methylation status, or radio/chemoresistance. Celecoxib and 2,5-DMC were the most cytotoxic. Cell cycle distribution was altered, and apoptosis was induced after the treatment with celecoxib, 2,5-DMC, etori- and valdecoxib in T98G cell line. COXIBs and 2,5-DMC did not influence MGMT methylation status, but inhibited COX-2/PGE2/EP4 pathway. Conclusions Not only celecoxib, but also 2,5-DMC, etori-, rofe- and valdecoxib should be further investigated as potential good anti-GBM therapeutics.

scholarly journals Cytotoxic Potential of the Coelomic Fluid Extracted from the Sea Cucumber Holothuria tubulosa against Triple-Negative MDA-MB231 Breast Cancer Cells

Biology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 76 ◽  
Author(s):  
Claudio Luparello ◽  
Debora Ragona ◽  
Dalia Maria Lucia Asaro ◽  
Valentina Lazzara ◽  
Federica Affranchi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Sea Cucumber ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Water Soluble ◽  
Coelomic Fluid ◽  
Cell Cycle Distribution ◽  
Widespread Species ◽  
Tnbc Cell

Growing evidence has demonstrated that the extracts of different holothurian species exert beneficial effects on human health. Triple negative breast cancers (TNBC) are highly malignant tumors that present a poor prognosis due to the lack of effective targeted therapies. In the attempt to identify novel compounds that might counteract TNBC cell growth, we studied the effect of the exposure of the TNBC cell line MDA-MB231 to total and filtered aqueous extracts of the coelomic fluid obtained from the sea cucumber Holoturia tubulosa, a widespread species in the Mediterranean Sea. In particular, we examined cell viability and proliferative behaviour, cell cycle distribution, apoptosis, autophagy, and mitochondrial metabolic/cell redox state. The results obtained indicate that both total and fractionated extracts are potent inhibitors of TNBC cell viability and growth, acting through both an impairment of cell cycle progression and mitochondrial transmembrane potential and a stimulation of cellular autophagy, as demonstrated by the increase of the acidic vesicular organelles and of the intracellular protein markers beclin-1, and total LC3 and LC3-II upon early exposure to the preparations. Identification of the water-soluble bioactive component(s) present in the extract merit further investigation aiming to develop novel prevention and/or treatment agents efficacious against highly metastatic breast carcinomas.

scholarly journals Quercetin modulates signaling pathways and induces apoptosis in cervical cancer cells

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Madhumitha Kedhari Sundaram ◽  
Ritu Raina ◽  
Nazia Afroze ◽  
Khuloud Bajbouj ◽  
Mawieh Hamad ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cancer Cells ◽  
Colony Formation ◽  
Epidemiological Data ◽  
Docking Studies ◽  
Extrinsic Pathway ◽  
M Cell ◽  
Cell Viability Assay ◽  
Wide Range

Abstract Cancer cells have the unique ability to overcome natural defense mechanisms, undergo unchecked proliferation and evade apoptosis. While chemotherapeutic drugs address this, they are plagued by a long list of side effects and have a poor success rate. This has spurred researchers to identify safer bioactive compounds that possess chemopreventive and therapeutic properties. A wide range of experimental as well as epidemiological data encourage the use of dietary agents to impede or delay different stages of cancer. In the present study, we have examined the anti-ancer property of ubiquitous phytochemical quercetin by using cell viability assay, flow cytometry, nuclear morphology, colony formation, scratch wound assay, DNA fragmentation and comet assay. Further, qPCR analysis of various genes involved in apoptosis, cell cycle regulation, metastasis and different signal transduction pathways was performed. Proteome profiler was used to quantitate the expression of several of these proteins. We find that quercetin decreases cell viability, reduces colony formation, promotes G2-M cell cycle arrest, induces DNA damage and encourages apoptosis. Quercetin induces apoptosis via activating both apoptotic pathways with a stronger effect of the extrinsic pathway relying on the combined power of TRAIL, FASL and TNF with up-regulation of caspases and pro-apoptotic genes. Quercetin could inhibit anti-apoptotic proteins by docking studies. Further, quercetin blocks PI3K, MAPK and WNT pathways. Anticancer effect of quercetin observed in cell-based assays were corroborated by molecular biology studies and yielded valuable mechanistic information. Quercetin appears to be a promising candidate with chemopreventive and chemotherapeutic potential and warrants further research.

Resveratrol induces cell cycle arrest and apoptosis in epithelioid malignant pleural mesothelioma cells

2017 ◽  
Vol 43 (2) ◽  
pp. 197-204
Author(s):  
Saime Batirel ◽  
Ergul Mutlu Altundag ◽  
Selina Toplayici ◽  
Ceyda Corek ◽  
Hasan Fevzi Batirel
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Malignant Pleural Mesothelioma ◽  
Cell Cycle Distribution ◽  
Pleural Mesothelioma ◽  
Dependent Manner ◽  
P53 Expression ◽  
Cycle Arrest

Abstract Background: Resveratrol is a natural anti-carcinogenic polyphenol. Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis. In this study, we investigated the effects of resveratrol on epithelioid MPM. Material and methods: Human epithelioid MPM cell line (NCI-H2452) was exposed to resveratrol (5–200 μM) for 24 or 48 h. Cell viability was assessed by WST-1 assay. Flow cytometry analyses were performed to evaluate the effects of resveratrol on cell cycle distribution and apoptosis. Western blot analysis was used to determine protein expression levels of antioxidant enzymes, cyclin D1 and p53. Reactive oxygen species (ROS) were measured using H2DCFDA. Results: Resveratrol reduced cell viability of the cells in a concentration and time dependent manner. After treatment, the cells accumulated in G0/G1 phase and the percentage of cells in G2/M phase was reduced. Resveratrol decreased cyclin D1 and increased p53 expression in cell lysates. Treated cells exhibited increased apoptotic activity. ROS were elevated with resveratrol treatment, but there was no change in the expression of superoxide dismutase (SOD)-1, SOD-2 and glutathione peroxidase. Conclusion: Our results revealed that resveratrol exhibits anti-cell viability effect on epithelioid MPM cells by inducing cell cycle arrest and apoptosis. Resveratrol may become a potential therapeutic agent for epithelioid MPM.

scholarly journals The Potential Application of Ecklonia cava Extract in Scalp Protection

Cosmetics ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. 9
Author(s):  
Hayeon Kim ◽  
Hyunju Woo ◽  
Seoungwoo Shin ◽  
Deokhoon Park ◽  
Eunsun Jung
Keyword(s):  
Cell Cycle ◽  
Clinical Trial ◽  
Cell Viability ◽  
Skin Barrier ◽  
Dermal Papilla ◽  
Ecklonia Cava ◽  
Cell Cycle Distribution ◽  
Dermal Papilla Cells ◽  
Airborne Pollutants ◽  
Urban Pollutants

The scalp is exposed to environmental hazards including airborne pollutants, which exert adverse effects on skin health. Therefore, compounds for defending skin from pollutants have attracted interest in the cosmeceutical community. We investigated whether Ecklonia cava exhibited prophylactic effects against urban pollutants by measuring cell viability and cell cycle distribution in human follicle dermal papilla cells (HFDPC). The effect of E. cava on pollutant-induced damage to skin barrier was determined by measuring filaggrin and MMP-1 expression in both keratinocytes and in a skin explant model. In a clinical trial, the effect of E. cava on scalp skin of patients with scalp scale was observed by evaluating hydration and redness after 4 weeks of daily treatment with a shampoo containing E. cava extract. E. cava extract recovered the loss of cell viability and abnormal cell cycle distribution induced by urban pollutants in HFDPCs. It also attenuated pollutant-induced damage to skin barrier by decreasing MMP-1 and increasing filaggrin expression in keratinocytes and the epidermis of skin explants. Moreover, E. cava showed soothing effects on human scalp by increasing hydration and decreasing redness in a clinical trial. Collectively, E. cava extract may be a good candidate for therapeutic applications designed to repair or protect hair scalp.

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