Flavonoids antitumor effects

In addition to their possible prooxidant activity (see above) polyphenols and flavonoids may influence cancer cells via their antioxidant properties. Recently, Jang et al. [219] studied cancer chemopreventive activity of resveratrol, a natural polyphenolic compound derived from grapes (Chapter 29). These authors showed that resveratrol inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Flavonoids silymarin and silibinin also exhibited antitumor-promoting effects at the stage I tumor promotion in mouse skin [220] and manifested antiproliferative effects in rat prostate cancer cells [221]. 

Although there are preliminary data supporting the antitumoral activity of quercetin, the most common flavonoid, in humans in the course of a Phase I clinical trial [189], direct evidence of the anticancer effect of flavonoids is derived almost exclusively from studies performed in animal models as well as studies performed on cultured cell lines, Fig. (2). Most animal studies on gastrointestinal cancer have focused on colon cancer using the azoxymethane (AOM) model in rats or mice [190-197]. There are also available reports on models of cancer of the stomach (induced by benzo[a]pyrene [198] or N-methyl-N-nitro-N-nitro so guanidine [199]), oesophagus (N-methyl-N-amylnitrosamine [200]), and the tongue/oral cavity (methyl-(acetoxymethyl)-nitrosamine [198], 7,12-dimethyl-... 

The spectrum of llavonoid biological effects is very broad the best known are their estrogenic, antitumor, antimicrobial, antiallergic, and antiinflammatory activities (for review, see Cushnie [19]). At least some of these activities are based on non-membrane-related mechanisms, like flavonoid-induced cell cycle arrest. Most of them, however, are claimed in the literature to appear as a consequence of antioxidative properties of flavonoids. 

The pharmacological activities of the various constituents of St.John s wort have been studied extensively. Hyperforin appears to be the major bioactive constituent and it acts in several ways serving as a neurotransmitter reuptake inhibitor with a broad selectivity, as a ligand for the pregnane X receptor, and as an antibacterial and antitumor agent. It also has a rapid effect on amyloid precursor protein processing, indicating a possible role in the prevention of Hypericin and the flavonoid constituents may have... 

Our studies on biologically active substances of this plant led to isolation of diterpenoids showing cytotoxicity [8], inhibitory effects on fi-glucuronidase [9], H+,K+-ATPase [10-12], replication of herpes simplex virus type 1 (HSV-1) [8,13,14] and bone resorption stimulated by parathyroid hormone (PTH) [15], and antitumor [16] and antitumor promoting effects [17]. In addition, some flavonoids possessing cytotoxicity [18], inhibitory activity against [3-glucuronidase [19] and antiviral activity [20] were also obtained from whole plants. 

Model M2 eomprises 57 medium-effective antitumor compoimds (3300 10- nM (class B) [14-15]. The value for a flavonoid baicalin, which has medium antitumor activity, served as a boundary criterion for the molecules of the M2 model training set between the classes of medium and low-effective compounds. The value of this substance amounts to 3330-16,300 nM for the above mentioned tumor cells. 

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