Antitumor Effects Of Quercetin Research Articles

Cytotoxicity, Proapoptotic Activity and Drug-like Potential of Quercetin and Kaempferol in Glioblastoma Cells: Preclinical Insights

Despite the increasing understanding of the pathogenesis of glioblastoma (GBM), treatment options for this tumor remain limited. Recently, the therapeutic potential of natural compounds has attracted great interest. Thus, dietary flavonoids quercetin (QCT) and kaempferol (KMF) were investigated as potential cytostatic agents in GBM. Moreover, the physicochemical properties of QCT and KMF, determining their bioavailability and therapeutic efficiency, were evaluated. We proved that both polyphenols significantly reduced the viability of GBM cells. We also demonstrated that both QCT and KMF evoked the cytotoxic effect in T98G cells via induction of apoptotic cell death as shown by increased activity of caspase 3/7 and caspase 9 together with an overexpression of the cleaved form of PARP. Apoptosis was additionally accompanied by the activation of stress responses in QCT- and KMF-treated cells. Both polyphenols caused oxidative stress and endoplasmic reticulum (ER) stress, as demonstrated by the increased generation of reactive oxygen species (ROS), deregulated expressions of superoxide dismutases (SOD2 and Sod1 on protein and transcriptomic levels, respectively), as well as an overexpression of ERO1α, GRP78, p-JNK, and an up-regulation of Chop, Atf4 and Atf6α genes. The antitumor effect of QCT and KMF was also confirmed in vivo, showing reduced growth of tumor xenografts in the chick chorioallantoic membrane (CAM) experiment. Moreover, electrophoretic light scattering (ELS) was used to measure the zeta potential of cell membranes upon exposition to QCT and KMF. Additionally, on the basis of existing physicochemical data, the drug-likeness score of QCT and KMF was evaluated. Analyses showed that both compounds accomplish Lipinski’s Rule of 5, and they both fit into the criteria of good central nervous system (CNS) drugs. Altogether, our data support the idea that QCT and KMF might be plausible candidates for evaluation as therapeutic agents in preclinical models of glioblastoma.

Quercetin inhibits the progression of endometrial HEC-1-A cells by regulating ferroptosis—a preliminary study

BackgroundEndometrial carcinoma (EC) is one of the most common female reproductive system tumors, which seriously threatens women's health. This preliminary study aimed to investigate the effects of quercetin on the EC cells and explore the potential mechanism.MethodsIn this study, the effects of quercetin on endometrial cancer HEC-1-A cells were studied by a series of cell biological methods, including CCK-8 detection of cell activity, Western blotting of ferroptosis-related proteins, apoptosis detection, reactive oxygen species (ROS) detection and other detections.ResultsOur results showed that quercetin inhibited the proliferation and migration of EC cells, induced cell apoptosis, and affected the cell cycle. Furthermore, the anti-tumor effect of quercetin was related to the induction of ferroptosis in the EC cells.ConclusionsOur study shows quercetin may exert anti-tumor effects, which may be related to the regulation of ferroptosis. Our study provides evidence for the future treatment of EC with small molecule drugs.

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review.

Quercetin is a flavonoid present in fruits, vegetables and plants with antioxidant, anti-inflammatory and anticancer properties. Its beneficial activities have been demonstrated in different human pathologies, including hepatoprotective effects against liver disorders. High mortality and late diagnosis of the primary liver tumor hepatocarcinoma (HCC) makes this cancer an interesting target for the study of quercetin effects. Our aim was to systematically review antitumor activities of quercetin in HCC preclinical studies employing single, encapsulated, combined or derived quercetin forms. Literature search was conducted in PubMed, Scopus and Web of Science (WOS), and 39 studies were finally included. We found that 17 articles evaluated quercetin effects alone, six used encapsulated strategy, 10 combined this flavonoid, two decided to co-encapsulate it and only four studied effects of quercetin derivatives, highlighting that only nine included in vivo models. Results evidence the quercetin antiproliferative and proapoptotic properties against HCC either alone and with the mentioned strategies; nevertheless, few investigations assessed specific activities on different processes related with cancer progression. Overall, further studies including animal models are needed to deeper investigate the precise mechanisms of action of quercetin as antitumor agent, as well as the potential of novel strategies aimed to improve quercetin effects in HCC.

Integrated Whole Transcriptome Profiling and Bioinformatics Analysis for Revealing Regulatory Pathways Associated With Quercetin-Induced Apoptosis in HCT-116 Cells.

Quercetin (QUE) is a bioactive component that belongs to the natural flavonoids group, and recent researchers found that it could prevent colorectal cancer (CRC). However, the exact mechanism by which QUE exerts its anti-tumor effects in CRC remains unclear. In this study, MTS assay and flow cytometry were used to detect the anti-tumor effects of QUE on HCT-116 cells. The results showed that QUE could inhibit the proliferation and induce apoptosis of HCT-116 cells. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. A total of 240 differentially expressed lncRNAs (DElncRNAs), 131 circRNAs (DEcircRNAs), 83 miRNAs (DEmiRNAs), and 1415 mRNAs (DEmRNAs) were identified in the QUE-treated HCT-116 cells compared to the untreated HCT-116 cells. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression of selected circRNAs, miRNAs, lncRNAs, and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to further investigate RNAs’ biological functions and potential mechanisms. Based on the theory of competing endogenous RNA (ceRNA), the circRNA–miRNA–mRNA and lncRNA–miRNA–mRNA regulatory networks were constructed to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Our results provided novel information about the molecular basis of QUE in treating CRC. Our findings indicated that deep RNA sequencing analysis of mRNA and ncRNAs was a promising approach to research anticancer mechanisms.

Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis

Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin can exert its anti-tumor function by regulating miR-22 together with miR-22 downstream pathway WNT1/β-catenin in OSCC. The results of Cell Counting Kit-8 (CCK-8) and flow cytometry analyses showed that quercetin treatment and miR-22 overexpression resulted in the reduction of cell viability and the increase of cell apoptotic rate in OSCC. WNT1 was a target of miR-22, which was confirmed by bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays. RT-qPCR assay showed that quercetin promoted miR-22 expression and suppressed WNT1 and β-catenin expression in OSCC cells, whereas this effect was abrogated by miR-22 inhibitor. Moreover, miR-22 depletion weakened quercetin-mediated viability inhibition and apoptosis increase in OSCC cells. Quercetin inhibited the growth of OSCC xenograft tumors by inducing miR-22 expression and repressing WNT1/β-catenin pathway in vivo. Taken together, quercetin hampered OSCC tumorigenesis by regulating miR-22/WNT1/β-catenin pathway in OSCC, providing a deep insight into the molecular targets of quercetin in the treatment of OSCC.

Antitumor effect of Quercetin on Y79 retinoblastoma cells via activation of JNK and p38 MAPK pathways

BackgroundQuercetin (QCT) is a flavonol present in many vegetables, it is proved to show chemo preventive effect against lung, cervical, prostate, breast and colon cancer due to its anti-inflammatory, anti-tumor and anti-oxidant property. Looking into the reported chemo-preventive effect we speculated antitumor activity in retinoblastoma (RB) Y79 cells, we also studied the molecular mechanism for antitumor activity.MethodsThe effect of QCT on Y79 cell viability count was done by cell counting kit, cell cycle distribution, apoptosis studies and mitochondrial membrane potential was evaluated by flow cytometry. Protein expression was done by western blot analysis.ResultsThe outcomes of study showed that QCT reduced Y79 cell viability and caused arrest of G1 phase in cell cycle via decreasing the expression levels of cyclin-dependent kinase (CDK)2/6 and cyclin D3 and by increasing the levels of both CDK inhibitor proteins p21 and p27. Apoptosis of Y79 cells mediated by QCT occurred via activation of both caspases-3/-9. Flow cytometry studies showed that QCT caused collapse in mitochondrial membrane potential (ΔΨm) in Y79 cells. Western blot studies confirmed that QCT brought about phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). We also established that inhibitors of JNK and p38 MAPK suppressed QCT mediated activation of both caspases-3/-9 and subdued the apoptosis of cancerous Y79 cells.ConclusionAll the results of the study suggest that QCT induced the apoptosis of Y79 cells via activation of JNK and p38 MAPK pathways, providing a novel treatment approach for human RB.

Quercetin 3-O-glucoside suppresses epidermal growth factor-induced migration by inhibiting EGFR signaling in pancreatic cancer cells.

Pancreatic cancer is one of the most dangerous cancers and is associated with a grave prognosis. Despite increased knowledge of the complex signaling networks responsible for progression of pancreatic cancer, many challenging therapies have fallen short of expectations. In this study, we examined the anti-migratory effect of quercetin 3-O-glucoside in epidermal growth factor-induced cell migration by inhibiting EGF receptor (EGFR) signaling in several human pancreatic cancer cell lines. Treatment with quercetin, quercetin 3-O-glucoside, and quercetin 7-O-glucoside differentially suppressed epidermal growth factor-induced migration activity of human pancreatic cancer cells. In particular, quercetin 3-O-glucoside strongly inhibited the infiltration activity of pancreatic cancer cells in a dose-dependent manner. Furthermore, quercetin 3-O-glucoside exerted the anti-migratory effect even at a relatively low dose compared with other forms of quercetin. The anti-tumor effects of quercetin 3-O-glucoside were mediated by selectively inhibiting the EGFR-mediated FAK, AKT, MEK1/2, and ERK1/2 signaling pathway. Combinatorial treatment with quercetin 3-O-glucoside plus gemcitabine showed the synergistic anti-migratory effect on epidermal growth factor-induced cell migration in human pancreatic cancer cell lines. These results suggest that quercetin 3-O-glucoside has potential for anti-metastatic therapy in human pancreatic cancer.

The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis

Background: The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin. Methods: The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression. Results: miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated. Conclusion: miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.