Novel coumarin derivatives containing a triazole moiety: A study on synthesis, cytotoxicity, membrane dysfunction, apoptosis, cell cycle, and antiangiogenic studies

2022 ◽  
Vol 22 ◽  
Author(s):  
Adem Güner ◽  
Hakan Bektaş ◽  
Emre Menteşe
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Dna Fragmentation ◽  
Human Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Vegf Expression ◽  
Gene Expressions ◽  
M Cell ◽  
Wide Range

Background: Coumarin is a functional compound with a pronounced wide range of biological activities and has recently been shown to have anticancer effects on various human cancer cells. Cisplatin is widely used in treating many cancers, but its effectiveness is limited due to acquired resistance and dose-related side effects. Objective: This study aimed to reveal the chemosensitizing ability of novel synthesized coumarin-triazole hybrid compounds (3a-f) compared to the cisplatin in A549, MCF-7, and HeLa cancer cells. Methods: Cytotoxicity was determined by MTT assay. Lactate dehydrogenase (LDH), antioxidant/oxidant status, DNA fragmentation were determined spectrophotometrically using commercial kits. Muse™ Cell Analyzer was used to assess cell cycle progression. Pro/anti-apoptotic gene expressions were determined by Real-Time qPCR. The antiangiogenic activity was determined by VEGF expression and Hen's chorioallantoic membrane model. Results: Compounds 3c, -d, -e, and -f potentiated the cisplatin-induced cytotoxicity through the increased LDH release and DNA fragmentation, induced G2/M cell cycle arrest, overproduction of oxidative stress, and decrease of cellular antioxidant levels. These compounds combined with cisplatin caused upregulation in the pro-apoptotic Bax, Bıd, caspase-3, caspase-8, caspase-9, Fas, and p53 gene expressions while downregulating anti-apoptotic DFFA, NFkB1, and Bcl2 gene expressions. These combinations caused vascular loss and a reduction in VEGF expression. Conclusion: These results suggest that a combinational regimen of coumarin compounds with cisplatin could be enhancing the effect of cisplatin in A549 cells. Besides, considering compounds have relatively low toxicity in normal cells, they decrease the dose requirement of cisplatin in cancer treatments.

scholarly journals Novel coumarin compounds potentiate the effect of cisplatin on lung cancer cells by enhancing pro-apoptotic gene expressions, G2/M cell arrest, oxidative and antiangiogenic effects

2021 ◽  
Author(s):  
Adem Güner ◽  
Hakan Bektaş ◽  
Emre Menteşe
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Dna Fragmentation ◽  
Acquired Resistance ◽  
Vegf Expression ◽  
Gene Expressions ◽  
M Cell ◽  
Apoptotic Gene ◽  
Wide Range ◽  
Coumarin Compounds

Coumarin is a functional compound with a pronounced wide range of biological activities and has recently been shown to have anticancer effects on various human cancer cells. Cisplatin is widely used in the treatment of many cancers but its effectiveness is limited due to acquired resistance and dose-related side effects. This study aimed to reveal the chemosensitizing ability of novel synthesized coumarin-triazole hybrid compounds (3a-f) alone or their combination with cisplatin in A549 cells.MTT assay was used for cytotoxic effects. Lactate dehydrogenase (LDH), antioxidant/oxidant status, DNA fragmentation were determined spectrophotometrically by using commercial kits. Muse™ Cell Analyzer was used to assess cell cycle progression. Pro/anti-apoptotic gene expressions were determined by Real-Time qPCR. The antiangiogenic activity was determined by VEGF expression and Hen's chorioallantoic membrane model. Compounds 3c, d, e, and f potentiated the cisplatin-induced cytotoxicity through the increase of LDH release and DNA fragmentation, induced G2/M cell cycle arrest, overproduction of oxidative stress, and decrease of cellular antioxidant levels. These compounds combined with cisplatin caused upregulation in the pro-apoptotic Bax, Bıd, caspase-3, caspase-8, caspase-9, Fas, and p53 gene expressions while downregulating anti-apoptotic DFFA, NFkB1, and Bcl2 gene expressions. These combinations caused vascular loss and a reduction in VEGF expression. These results suggest that a combinational regimen of coumarin compounds with cisplatin overcome the acquired resistance of cancer cells to cisplatin and, considering compounds have relatively low toxicity in normal cells, decrease the dose requirement of cisplatin in cancer treatments.

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.

The novel anthraquinone derivative IMP1338 induces death of human cancer cells by p53-independent S and G2/M cell cycle arrest

2016 ◽  
Vol 79 ◽  
pp. 308-314 ◽  
Author(s):  
Hyun Kyung Choi ◽  
Hwani Ryu ◽  
A-rang Son ◽  
Bitna Seo ◽  
Sang-Gu Hwang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Cancer ◽  
The Novel ◽  
M Cell ◽  
Anthraquinone Derivative ◽  
Human Cancer Cells ◽  
Cycle Arrest

A small molecule IFB07188 inhibits proliferation of human cancer cells by inducing G2/M cell cycle arrest and apoptosis

2012 ◽  
Vol 66 (7) ◽  
pp. 512-518 ◽  
Author(s):  
Tingzhe Sun ◽  
Wei Zheng ◽  
Hui Peng ◽  
Aihua Zhang ◽  
Yongjun Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Human Cancer ◽  
M Cell ◽  
Human Cancer Cells ◽  
Cycle Arrest

Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia

2009 ◽  
Vol 25 (8) ◽  
pp. 505-515 ◽  
Author(s):  
Qu Ge-ping ◽  
Xiu Qing-Yu ◽  
Li Bing ◽  
Liu Yong-an ◽  
Zhang Ling-Zhen
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Cyclin B ◽  
M Cell ◽  
Cycle Arrest ◽  
Induction Of Apoptosis

Arsenic trioxide (As 2O3) has been established to be an effective agent for treating acute promyleocytic leukemia. Laboratory data suggest that As2O 3 induces apoptosis of several solid tumor cells including lung cancer cells. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we studied the cytotoxic effect of As2O3 on human lung adenocarcinoma cell lines A549 and A549/R (resistant to vincristine, adriamycin and mitomycin etc.) grown under normoxic and hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 5, 10 and 15 µM As2O3 induced evident growth inhibition and apoptosis in A549 cells as well as A549/R cells after 48 hours of exposure. In contrast, the conventional chemotherapeutic drug vincristine showed lowered efficiency in hypoxic A549 cells. As2O3 induced G2/M cell cycle arrest in both normoxic and hypoxic A549 cells. As2O3 significantly decreased the messenger RNA (mRNA) levels of Cyclin B1 and survivin and the protein levels of Cyclin B1, phospho-CDC2 (Thr 161) and survivin in both normoxic and hypoxic A549 cells. Together, our findings indicated that As2O3 significantly inhibited the proliferation of lung cancer cells via G2/M cell cycle arrest and induction of apoptosis at both normoxia and hypoxia, and the induction of apoptosis was associated with down regulation of survivin.

Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

2019 ◽  
Vol 19 (9) ◽  
pp. 1132-1140
Author(s):  
Heba A.E. Mohamed ◽  
Hossa F. Al-Shareef
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cytotoxic Activities ◽  
Significant Group ◽  
Design Synthesis ◽  
Standard Drug ◽  
Wide Range

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

A resveratrol analog, phoyunbene B, induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells

2012 ◽  
Vol 22 (5) ◽  
pp. 2114-2118 ◽  
Author(s):  
Guanghui Wang ◽  
Xiaoyu Guo ◽  
Haifeng Chen ◽  
Ting Lin ◽  
Yang Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
M Cell ◽  
Liver Cancer Cells ◽  
Cycle Arrest
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