Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway

Abstract

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G₀/G₁ phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

Keywords

quercetin / HeLa cells / PI3K / p-AKT / Bc1-2 / Bax

References

[1] FerlayJ, ShinHR, BrayF, et al. . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 2010, 127(12): 2893-2917 PMID: 21351269

[2] VapiwalaN, MickR, HampshireMK, et al. . Patient initiation of complementary and alternative medical therapies (CAM) following cancer diagnosis. Cancer J, 2006, 12(6): 467-474 PMID: 17207316

[3] ChirumboloS. Quercetin in cancer prevention and therapy. Integr Cancer Ther, 2013, 12(2): 97-102 PMID: 22740081

[4] RussoM, SpagnuoloC, TedescoI, et al. . The flavonoid quercetin in disease prevention and therapy: Facts and fancies. Biochem Pharmacol, 2012, 83(1): 6-15 PMID: 21856292

[5] JungJH, LeeJO, KimJH, et al. . Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation. J Cell Physiol, 2010, 223(2): 408-414 PMID: 20082303

[6] WangP, ZhangK, ZhangQ, et al. . Effects of quercetin on the apoptosis of the human gastric carcinoma cells. Toxicol In Vitro, 2012, 26(2): 221-228 PMID: 22222411

[7] ChouCC, YangJS, LuHF, et al. . Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway. Arch Pharm Res, 2010, 33(8): 1181-1191 PMID: 20803121

[8] BenbrookDM, MasamhaCP. The pro-survival function of Akt kinase can be overridden or altered to contribute to induction of apoptosis. Curr Cancer Drug Targets, 2011, 11(5): 586-599 PMID: 21486222

[9] WalkerEH, PacoldME, PerisicO, et al. . Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell, 2000, 6(4): 909-919 PMID: 11090628

[10] DuoJ, YingGG, WangGW, et al. . Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation. Mol Med Rep, 2012, 5(6): 1453-1456 PMID: 22447039

[11] Vidya PriyadarsiniR, Senthil MuruganR, MaitreyiS, et al. . The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol, 2010, 649(1–3): 84-91 PMID: 20858478

[12] ZhuangJ, HawkinsSF, GlennMA, et al. . Akt is activated in chronic lymphocytic leukemia cells and delivers a pro-survival signal: the therapeutic potential of Akt inhibition. Haematologica, 2009, 95(1): 110-118 PMID: 19713228 PMCID: 2805750

[13] ChengS, GaoN, ZhangZ. Quercetin induces tumor-selective apoptosis through downregulation of Mcl-1 and activation of Bax. Clin Cancer Res, 2010, 16(23): 5679-5691 PMID: 21138867 PMCID: 3069720