Quercetin and Cancer Chemoprevention

Abstract

Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as “chemopreventers”. Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health.

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

“…As an antioxidant it possesses the most potent ROS scavenging activity and provides protection against the development of variety of cancers by ameliorating ROS-mediated cellular damages [187] . Moreover, it reduces the level of oxidative enzymes, such as xanthine oxidase (XOD), lipoxygenase and NADPH oxidase, thereby preventing free radical-induced cellular damage [187] . In vivo studies have been performed to depict the chemopreventive properties of quercetin on different cancers.…”

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

“…These finding support that p38 MAPK plays a critical role in FEOJ-induced apoptosis. In addition, the merit of FEOJ as compared to the quercetin is that the bioavailability of quercetin in FEOJ is much better that that quercetin aglycone (Manach et al, 2005;Gibellini et al, 2011), because quercetin in FEOJ is in the form of quercetin glucosides, which are easily absorbed in the apical membrane of enterocyte (O'Leary et al, 2003).…”

Bracken-fern Extracts Induce Cell Cycle Arrest and Apoptosis in Certain Cancer Cell Lines

“…The variation in responses could be due to the presence of several differently active constituents in the crude BFE. The BFE, used in this experiment, may contain different components (Wilson et al, 1998) for example Quercetin (Qu), the major dietary flavonoid, which present in bracken fern (Gibellini et al, 2011) has anti-proliferative and pro-apoptotic effects. We tend to suggest that the BFE may contain high amounts of Qu.…”

“…Qu has been accepted as pro-apoptotic flavonoid with a special and nearly exclusive activity on tumor cell lines rather than normal cells (Lugli et al, 2009). Therefore, based on its major effects, this component is generally known as pro-apoptotic and cell cycle regulator (Gibellini et al, 2011). These properties are believed to be connected to the ability of Qu in targeting tubulins, which lead to depolymerization of the cellular microtubules (Gupta and Panda, 2002).…”

“…Depending on the cell type and tumor origin, Qu is capable to arrest the cell cycle at G2/M or at the G1/S transition (Gibellini et al, 2011). Based on the fact, that BFE caused DNA damage and apoptosis at high concentrations (200 µg/mL on TCC cells) and also it probably induce cell cycle arrest at mild concentrations (50 and 30 µg/mL) depending on the cell type and tumor origin.…”