Polyphenolic compounds are widely distributed in the vegetable kingdom and are therefore consumed regularly in the human diet. Epidemiological studies suggest that foods rich in polyphenolic compounds contribute to reducing the risk of cancer. The purpose of our work is to: 1) study the possible cytotoxicity and antiproliferative effects of 13 polyphenolic compounds on 3 cell lines of melanocytes, 2 of melanoma (B16F10 and SK-MEL-1), and 1 of nontransformed melanocytes (Melan-a); and 2) identify the possible relationship between the chemical structure of the tested compounds and their effect on cellular viability. The said polyphenolic compounds corresponded to 8 flavonoids with varying hydroxyl and methoxyl substituents, related structurally through the oxidation state of their flavonoid skeleton, a catechin polymer and 4 phenolic acids. The cytotoxic activity of all the studied compounds was modest or not apparent. The flavonoids luteolin, tangeretin, baicalein, quercetin, and myricetin, and g...

Although flavonoids seem to be capable of acting at all stages of the carcinogenic process, little information is available on their action in melanoma cell lines. The aim of this study was to assess the response of B16F10 and SK-MEL-1 melanoma cell lines to treatment with six different flavonoids after 24 and 72 h of exposure and to relate the response to their structure. We then compared the findings with those for melphalan treatment. When cultures were treated for 24 h, only slight inhibition at the highest concentrations (25 and 50 μM) of tangeretin and luteolin were observed, whereas melphalan caused a dose-related inhibition of growth at all concentrations. Quercetin, hesperetin, 7,3′-dimethylhesperetin and eriodictyol did not produce any effect at 24 h on B16F10 or SK-MEL-1 cells, results which point to the low toxicity of flavonoids. After 72 h of exposure culture growth was inhibited by 7,3′-dimethylhesperetin at 50 μM, but lower concentrations had no effect. Tangeretin was the most effective of the flavonoids in inhibiting B16F10 and SK-MEL-1 cell growth, showing a clear dose–response curve after 72 h. These results suggest that the absence of the C2–C3 double bond on hydroxylated flavonoids results in a loss of effect on both the cell lines, while the higher activity of tangeretin compared with 7,3′-dimethylhesperetin suggests that the presence of at least three adjacent methoxyl groups confers a more potent antiproliferative effect.

Attempts to control cancer involve a variety of means, including the use of suppressing, blocking and transforming agents. Suppressing agents prevent the formation of new cancers from pro-carcinogens, blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or to prevent their biological actions. Flavonoids can act as all three types of agent. Epidemiological and animal studies suggest that flavonoids have a protective effect against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely understood. In recent years, experimental studies have provided growing evidence supporting the beneficial action of flavonoids on multiple cancer-related biological pathways (carcinogen bio-activation, cell-signaling, cell cycle regulation, angiogenesis and inflammation). Within the last decade, reports on flavonoid activity have largely associated with enzyme inhibition and anti-proliferative activity. Many of these studies have pointed to a structural-functional relationship, in that the antioxidant, enzyme-inhibition or antiproliferative activities of flavonoids are dependent on particular structural motifs. Our own studies have shown that structural factors would explain the antioxidant, antiproliferative and antimetastasic properties of some citrus flavonoids. In this paper we discuss the relation between each structural factor and the anticancer activity of Citrus flavonoids.

The radioprotective effects of a polyphenolic extract of Olea europaea L. leaves (OL); the flavonoids diosmin and rutin, which are widely used as pharmaceuticals; and the sulfur-containing compounds dimethylsulfoxide (DMSO) and 6-n-propyl-2-thiouracil (PTU) were determined by using the micronucleus test for anticlastogenic activity, evaluating the reduction of the frequency of micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow of mouse before and after X-ray irradiation. With treatment before X-irradiation, the most effective compounds were, in order, rutin > DMSO > OL > PTU > diosmin. These results showed, for the polyphenols studied, a linear correlation (r² = 0.965) between anticlastogenic activity and antioxidant capacity. The magnitude of protection with treatment after X-irradiation were lower, and the most effective compounds were, in order, OL > diosmin > rutin; DMSO and PTU lacked radioprotective activity. Therefore, OL is the only substance that showed a significant anticlastogenic activity both before and after X-ray irradiation treatments. Structurally, the free oxygen radicals and lipoperoxyradicals scavenging capacity and, consequently, the anticlastogenic activity of these polyphenolic compounds are based principally on the presence of specific functional groups, mainly catechol groups (rutin, oleuropein, hydroxytyrosol, verbascoside, luteolin), that also increase the stability of the aroxyl-polyphenol radical generated in the above processes.