Quercetin-Induced Apoptosis in Colorectal Tumor Cells: Possible Role of EGF Receptor Signaling

Richter, M.; Ebermann, Robert; Marian, Brigitte

doi:10.1207/s15327914nc340113

Cited by 147 publications

(74 citation statements)

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“…QC has also been shown to down-regulate or inhibit the phosphatidylinositol and phosphatidylinositol phosphate kinase activities in human carcinoma cells, leading to a marked reduction in second messenger IP3 concentration and cell death (9,10). Therefore, QC may be useful in the treatment of carcinomas with increased or down-regulated signal transduction capacity (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549

Zheng

Yin²,

Jiang

et al. 2011

Mol Med Report

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Abstract. The aim of the present study was to investigate the anticancer effect of quercetin (QC) in the human lung cancer cell line A-549 and further study the mechanism of apoptosis induction by QC. Low differentiation potential A-549 human lung cancer cells were treated with QC at different doses and for different times, and the growth inhibitory rates were detected by MTT assay. Apoptosis induced by QC in A-549 cells was observed by Annexin V/PI double staining and flow cytometric assay. The relative tumor growth ratio of the treated/control tumors (T/C) (%) was chosen to represent the tumor growth inhibition of A-549 cell nude mouse xenografts by QC. Apoptosis of the nude mouse xenografts was observed by Annexin V/PI double staining and flow cytometric assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by QC, changes in the expression of bcl-2 and bax genes were detected by RT-PCR. Following incubation with QC, the cell growth of the low differentiation potential A-549 human lung cancer cells was dramatically inhibited in a dose-dependent manner. After the cells were exposed to QC for 24, 48 and 72 h, the IC 50 value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 µmol/l, respectively. Apoptosis in the A-549 cells induced by QC was noted. The apoptotic subpopulation of A-549 cells was approximately 12.96 and 24.58%, respectively, when cells were incubated with 1.2 µmol/l QC for 48 and 72 h. T/C (%) of A-549 nude mouse xenografts was 44.3, when the nude mice were treated with QC (8 mg/kg). Meanwhile, apoptosis induced by QC was observed in the A-549 nude mouse xenografts. Increased expression of the bax gene and decreased expression of the bc1-2 gene were noted using RT-PCR. Our results provide further evidence of the growth inhibition of the A-549 human lung adenocarcinoma cancer cell line by QC. This effect is associated with the induction of apoptosis in A-549 cells and the molecular mechanism may be related to the reduction in expression of the apoptosis-regulating gene bcl-2, and increase in expression of the apoptosis-regulating gene bax. These results were also confirmed in vivo.

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Section: Introductionmentioning

confidence: 99%

Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549

Zheng

Yin²,

Jiang

et al. 2011

Mol Med Report

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“…The bioactivities of quercetin are complex and include antioxidative, antiviral, antibacterial and anti-inflammatory effects (4,6,7). Recently, quercetin was found to possess strong anticancer properties in colon cancer (8)(9)(10)(11), breast cancer (12,13), leukemia (14)(15)(16), hepatocellular carcinoma (17), pancreatic carcinoma (18), salivary adenoid cystic carcinoma (19) and lung cancer (20). Although the anti-tumor effects of quercetin have been examined in several tumors, very little is known about its effects in osteosarcoma cells.…”

Section: Introductionmentioning

confidence: 99%

Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt

Xie

Yin²,

Jia

et al. 2011

Oncol Rep

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Abstract. Quercetin is the most abundant polyphenolic flavonoid found in plants. Several studies suggest that it has potent anticancer effects. The present study examines the apoptosisinducing activity and the underlying mechanism of action of quercetin in a methotrexate (MTX)-resistant osteosarcoma model. Our results showed that quercetin inhibited cell viability in a dose-dependent manner and there was no cross-resistance between MTX and quercetin in U2-OS/MTX300 cells. The induction of apoptosis was observed by flow cyto metry and fluorescence staining experiments. Quercetin-induced apoptosis was accompanied by a significant reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, activation of caspase-3, down-regulation of Bcl-2, p-Bad and up-regulation of Bax. A remarkable dephosphorylation of Akt was also detected after quercetin treatment. Furthermore, transduction with constitutively active Akt protected against the quercetin-induced dephosphorylation of Akt and Bad as well as poly(ADP-ribose)polymerase (PARP) degradation, while combined treatment with quercetin and LY294002 enhanced the dephosphorylation of Akt, Bad and PARP cleavage in U2-OS/MTX300 cells. Taken together, our results demonstrate that quercetin-induced apoptosis in the MTX-resistant osteosarcoma cells U2-OS/MTX300 was mediated via mitochondrial dysfunction and dephosphorylation of Akt. IntroductionOsteosarcoma is the most common primary malignant bone tumor diagnosed in children and adolescents (1). Due to the development of adjuvant and neo-adjuvant chemotherapy, local control of osteosarcoma and overall survival have improved significantly. Currently used chemotherapy regimens are based on a combination of methotrexate (MTX), doxorubicin, cisplatin and ifosfamide. MTX is the most active one (2). Despite improvements of chemotherapy, a considerable number of osteosarcoma patients develop MTX resistance and die as a result of disease progression (3). Additional therapeutic agents should be evaluated to improve the survival of MTX-resistant osteosarcoma patients.Quercetin is the most abundant molecule in the extensive class of polyphenolic flavonoids and is found ubiquitously in plants and foods (4). The average daily dietary intake of quercetin is estimated to be 16 mg (5). The bioactivities of quercetin are complex and include antioxidative, antiviral, antibacterial and anti-inflammatory effects (4,6,7). Recently, quercetin was found to possess strong anticancer properties in colon cancer (8-11), breast cancer (12,13), leukemia (14-16), hepatocellular carcinoma (17), pancreatic carcinoma (18), salivary adenoid cystic carcinoma (19) and lung cancer (20). Although the anti-tumor effects of quercetin have been examined in several tumors, very little is known about its effects in osteosarcoma cells. Thus, in this study we used a MTX-resistant model to determine the effects of quercetin on the MTX-resistant osteosarcoma cells, and elucidate the underlying mechanism. MTT assay. After quercetin trea...

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“…Quercetin, one of the most abundant flavonoids present in leaf vegetables and teas ( 7 ), has a wide range of biological effects such as antiatherogenic effects ( 8 , 9 ), antiproliferative effects on many cancer cell lines (10)(11)(12), and amelioration of metabolic syndrome abnormalities, which include obesity, dyslipidemia, insulin resistance, and hypertension ( 8 , 13-15 ). These beneficial effects have been attributed mainly to quercetin's antioxidative potency and protein-function modulating activity.…”

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confidence: 99%

Quercetin Enhances VDR Activity, Leading to Stimulation of Its Target Gene Expression in Caco-2 Cells

Inoue

Choi

Yoshidomi

et al. 2010

J Nutr Sci Vitaminol

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Summary Vitamin D receptor (VDR) is a nuclear receptor that regulates the expression of genes involved in calcium homeostasis. Activation of VDR is thought to be a promising drug target for osteoporosis. Using a VDR-driven luciferase expression assay for screening a naturally occurring food component, we identified quercetin as a VDR activator. Quercetin also activated the GAL4 DNA-binding domain fused to the VDR ligand-binding domain. Moreover, it was confirmed that quercetin increases the mRNA level of TRPV6, which is a VDR target gene, in Caco-2 cells. These results indicate that quercetin enhances VDR activity through the alteration of cofactor recruitment, thereby stimulating its target genes while providing a new function for quercetin as the VDR activator.

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Quercetin-Induced Apoptosis in Colorectal Tumor Cells: Possible Role of EGF Receptor Signaling

Cited by 147 publications

References 0 publications

Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549

Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549

Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt

Quercetin Enhances VDR Activity, Leading to Stimulation of Its Target Gene Expression in Caco-2 Cells

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