Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

Yousuf, Mohd; Khan, Parvez; Shamsi, Anas; Shahbaaz, Mohd; Hasan, Gulam Mustafa; Haque, Qazi Mohd Rizwanul; Christoffels, Alan; Islam, Asimul; Hassan, Md. Imtaiyaz

doi:10.1021/acsomega.0c03975

Cited by 51 publications

(20 citation statements)

References 84 publications

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“…Que can induce G2/M cell cycle arrest in numerous cancer cell lines through the regulation of cycle related molecules such as cyclinB1, MiR-34a, and p53 (Lou et al., 2015 ). In addition, Que displays a high binding affinity to CDK6 and downregulates its expression in A549, arresting cell cycle and reducing cell viability and colony formation (Yousuf et al., 2020 ). In this study, free Que treatment showed a slight arrest in G2/M, about 2.84% and 5.28% at concentration of 5 and 10 µg/mL, respectively.…”

Section: Resultsmentioning

confidence: 99%

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Zang

Meng

et al. 2022

Drug Delivery

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Lung cancer is the leading cause of cancer death world-wide and its treatment remains a challenge in clinic, especially for non-small cell lung cancer (NSCLC). Thus, more effective therapeutic strategies are required for NSCLC treatment. Quercetin (Que) as a natural flavonoid compound has gained increasing interests due to its anticancer activity. However, poor water solubility, low bioavailability, short half-life, and weak tumor accumulation hinder in vivo applications and antitumor effects of Que. In this study, we developed Que-loaded mixed micelles (Que-MMICs) assembled from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–poly(ethylene glycol)–biotin (DSPE–PEG–biotin) and poly(ethylene glycol) methyl ether methacrylate–poly[2-(dimethylamino) ethyl acrylate]–polycaprolactone (PEGMA–PDMAEA–PCL) for NSCLC treatment. The results showed that Que was efficiently encapsulated into the mixed micelles and the encapsulation efficiency (EE) was up to 85.7%. Cellular uptake results showed that biotin conjugation significantly improved 1.2-fold internalization of the carrier compared to that of non-targeted mixed micelles. In vitro results demonstrated that Que-MMICs could improve cytotoxicity (IC 50 = 7.83 μg/mL) than Que-MICs (16.15 μg/mL) and free Que (44.22 μg/mL) to A549 cells, which efficiently induced apoptosis and arrested cell cycle. Furthermore, Que-MMICs showed satisfactory tumor targeting capability and antitumor efficacy possibly due to the combination of enhanced permeability and retention (EPR) and active targeting effect. Collectively, Que-MMICs demonstrated high accumulation at tumor site and exhibited superior anticancer activity in NSCLC bearing mice model.

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Section: Resultsmentioning

confidence: 99%

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Zang

Meng

et al. 2022

Drug Delivery

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“…Quercetin (3,3′,4′5,7-pentahydroxyflavone), classified as a flavonoid, is found in many plants and foods consumed by humans such as apples, berries, grape, onions, green tea, and Ginkgo biloba. A polyphenolic compound, quercetin, presents a variety of physiological benefits, including anti-oxidant, anti-inflammatory, anti-cancerous, anti-viral, anti-bacterial, and immunomodulatory [49] , [111] , [112] , [113] , [114] , [115] . Studies including in vitro system and in vivo animal model have shown the immune-modulating effects of quercetin, such as an increase in the chemotaxis motion of neutrophil cells, phagocytosis, lytic activity and proliferation of different immune cells.…”

Section: Quercetin Mediated Inhibition Of 3cl Protease Activity and Viral Entrymentioning

confidence: 99%

Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights

Ali

Alam

Khatoon

et al. 2022

Biomedicine & Pharmacotherapy

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The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.

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“…CDK6 was cloned, expressed, and purified by following our previously published protocols 78,79 . The purity of the recombinant CDK6 protein was checked on 12% sodium dodecyl sulfate‐polyacrylamide gel electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

Targeting cyclin‐dependent kinase 6 by vanillin inhibits proliferation of breast and lung cancer cells: Combined computational and biochemical studies

Yousuf

Shamsi

Queen

et al. 2021

J of Cellular Biochemistry

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Cyclin‐dependent kinase 6 (CDK6) is a member of serine/threonine kinase family, and its overexpression is associated with cancer development. Thus, it is considered as a potential drug target for anticancer therapies. This study showed the CDK6 inhibitory potential of vanillin using combined experimental and computational methods. Structure‐based docking and 200 ns molecular dynamics simulation studies revealed that the binding of vanillin stabilizes the CDK6 structure and provides mechanistic insights into the binding mechanism. Enzyme inhibition and fluorescence‐binding studies showed that vanillin inhibits CDK6 with an half maximal inhibitory concentration = 4.99 μM and a binding constant (K) 4.1 × 107 M−1. Isothermal titration calorimetry measurements further complemented our observations. Studies on human cancer cell lines (MCF‐7 and A549) showed that vanillin decreases cell viability and colonization properties. The protein expression studies have further revealed that vanillin reduces the CDK6 expression and induces apoptosis in the cancer cells. In conclusion, our study presents the CDK6‐mediated therapeutic implications of vanillin for anticancer therapies.

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Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

Cited by 51 publications

References 84 publications

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights

Targeting cyclin‐dependent kinase 6 by vanillin inhibits proliferation of breast and lung cancer cells: Combined computational and biochemical studies

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