Quercetin is an important dietary flavonoid, present in vegetables, fruits, seeds, nuts, tea and red wine. It has various biological functions in terms of tumor prevention. Quercetin is a strong inhibitor of PI3K, NF-κB, and other kinases involved in intracellular signaling. It can also mildly inhibit Akt1/2, and slightly affect PKC, p38 and ERK1/2 [1].
A number of reports have demonstrated that Quercetin possessed anti-inflammatory, anti-oxidant and pro-apoptotic functions in cancer cells and inhibited tumor progress with different mechanisms. Quercetin increased cytosolic Ca2+ levels and disrupted the mitochondrial membrane potential (MMP), which in turn promoted the release of cytochrome c in the cytoplasm, thus activating multiple caspases such as caspase-3, -8 and -9 and subsequently inducing apoptosis via mitochondrial pathway [2]. Quercetin induced cell-cycle arrest and apoptosis, which was associated with the function of p53. Quercetin could promote p53 phosphorylation and therefore stabilize p53 both at the mRNA and protein level [3]. However, several studies investigated that cells with impaired p53 became more sensitive to Quercetin mediated cytotoxicity and apoptosis [4].
In vivo studies showed that administration of Quercetin before the initiation stage of carcinogenesis dramatically reduced various chemical agents induced tumor burden in mice models, including benzo(a)pyrene-induced lung tumor burden, azoxymethane-induced preneoplastic lesions in rat colon and N-nitrosodiethylamine-induced hepatocarcinoma etc. [5].
槲皮素是一种重要的膳食类黄酮，在蔬菜、水果、种子、坚果、茶叶和红酒中均有分布。它在肿瘤预防方面具有各种生物学功能。槲皮素是PI3K、NF-κB和其他参与细胞内信号转导的激酶的强力抑制剂。它也能轻微抑制Akt1/2，并轻微影响PKC、p38和ERK1/2等 [1]。
许多报告已经证明，槲皮素在癌细胞中具有抗炎、抗氧化和促凋亡等功能，并通过不同的机制抑制肿瘤进展。槲皮素提高了细胞质中Ca2+水平并破坏了线粒体膜电位(MMP)，从而促进了细胞质中细胞色素c的释放，激活多种半胱氨酸蛋白酶如半胱氨酸蛋白酶-3、-8和-9，并随后通过线粒体途径诱导细胞凋亡[2]。槲皮素诱导细胞周期停滞和凋亡，与p53的功能有关。槲皮素可以促进p53磷酸化，因此在mRNA和蛋白质水平上稳定p53 [3]。然而，一些研究表明，p53功能受损的细胞对槲皮素介导的细胞毒性和凋亡更为敏感[4]。
体内研究表明，在癌变发生前期给予槲皮素，能显著降低小鼠模型中各种化学物质引起的肿瘤负担，包括苯并(a)芘诱导的肺肿瘤负担、氧化甲基异腺嘌呤诱导的大鼠结肠癌前病变和N-亚硝基二乙胺诱导的肝癌等[5]。
References:
[1].Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med. 2011;2011:591356. doi: 10.1093/ecam/neq053. Epub 2011 Apr 14.
Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. Int J Cancer. 2002 Apr 10;98(5):761-9.
[2].Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells. Bioscience, Biotechnology and Biochemistry. 2008;72(3):797–804.
[3].Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. The Journal of Biological Chemistry. 2004
[4].The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene. Biological and Pharmaceutical Bulletin. 2007