Quercetin

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].

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