Abstract
Objective To investigate the effect of quercetin on cell proliferation and apoptosis of MCF-7 human breast cancer cells, and effects of signaling pathways of PTEN/PI3K/AKT and c-Jun N-terminal kinase (JNK) signaling pathway. Methods MCF-7 cells were treated with quercetin (0, 20, 40, 60, 80, 100 μmol/L) CCK-8 assay was used to detect the cell proliferation, and cell apoptosis was assayed by flow cytometry. Hochesst33342 staining was used to observe the changes of nuclear number and karyotype, and flow cytometry was employed to detect cell apoptosis. The expression of PTEN and phosphorylated JNK (p-JNK) were detected by immunofluorescence cytochemistry, and the protein levels of PTEN, phosphorylated PI3K (p-PI3K), p-JNK and phosphorylated AKT (p-AKT) were detected by Western blot analysis. After treated with PI3K/AKT pathway inhibitor LY294002, the cell apoptosis and related protein expression were detected by the above methods again. Results With increased quercetin concentration, cell activity decreased and cell growth was inhibited in a concentration dependent manner; the nuclear concentration and apoptosis also increased. High concentration of quercetin significantly enhanced the expression and distribution of PTEN protein, decreased the levels of p-PI3K and p-AKT protein, and inhibited the expression of p-JNK protein. After adding LY294002 to inhibit PI3K/AKT, the apoptosis rate increased for cells treated with both LY294002 and quercetin; the expression of PTEN protein also showed an increase. Quercetin could significantly enhance the effect of LY294002 on p-PI3K/AKT/PTEN protein. Conclusion Quercetin can signeristically inhibit cell viability and induce cell apoptosis on MCF-7 cells, by up-regulating the expression of PTEN and down-regulating PI3K/AKT and JNK pathways.
