Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor (IGF)-1 signaling in mouse skin cancer

Abstract

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

Quercetin: A Promising Flavonoid with a Dynamic Ability to Treat Various Diseases, Infections, and Cancers

“…Inflammation via activation and recruitment of immune cells in addition to late-phase reactions describe the primary function mast cell secretions [123] [124]. Quercetin Cannabinoid receptor [36] Death Receptor [102] Survivin [102] EGF [106] IGF [103] p53 [104] p21 [105] has been shown to attenuate the activation of the transcription factor NF-κB which in turn inhibits the downstream expression of TNF-α, IL-1, IL-6, and IL-8 [41]. Activation of cytokines in mast cells via IgE-mediated mast cell activation was also inhibited by concentrated extract containing significant levels of quercetin [125].…”

Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa

“…tomatoes, grapes, onions and apples) as well as in tea and wine (Boots et al 2008;Kumar et al 2009;Lee and Mitchell 2012). There are several health and physiological benefits of QCT administration including cardioprotective, anticarcinogenic, antioxidant, antiapoptotic and ergogenic effects (Casuso et al 2013;Chen et al 2013;Jung et al 2013;Ravichandran et al 2014;Yang et al 2014). QCT exerts a certain level of activity against planktonic bacteria, such as Streptococcus mutans; however, it is active only at higher concentrations in some planktonic bacteria, and for others, it may not be active at any concentration (Martini et al 2004;Eumkeb and Chukrathok 2013;Patra et al 2014).…”

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

“…Antiproliferative effect : Quercetin has been shown to inhibit TGF‐α and EGF‐induced human prostate cancer cell proliferation . Similarly, quercetin suppressed IGF‐1‐induced phosphorylation of IGF‐1R, insulin receptor substrate‐1, AKT, and S6K, and inhibited IGF‐1‐stimulated proliferation of mouse skin cancer cells . The antiproliferative effect of quercetin was also mediated by induction of apoptosis and/or cell cycle arrest via modulation of multiple signaling pathways [AMP‐activated protein kinase, NF‐κB, and signal transducer and activator of transcription] in wide variety of cancer cells.…”