Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways

Abstract

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 antimetastatic properties of some citrus flavonoids. In this paper we discuss the relation between each structural factor and the anticancer activity of Citrus flavonoids.

<i>Citrus</i> Flavonoids and Human Cancers

“…It has been suggested that flavonoids-rich diet has an adverse effect on the proliferation of cancer cells [94,95].Various mechanisms have been proposed to explain the anti-proliferative activity of flavonoids, for example, it has been proposed that the anti-proliferative effects of flavonoids are mainly mediated by the inhibition on several kinases and kinase inhibitors involved in cellcycle arrest and apoptosis [85]. Cyclin-dependent kinases (CDKs) have been recognized as key regulators of cell cycle progression.…”

Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma

“…Targeting AKT-p53 network through RARγ may provide a new therapeutic method. Since flavonoids represent a large class of naturally occurring active compounds contained in food and medicinal plants 21 and have been shown to have potential to combat HCC 42 . Our findings suggest that RARγ-based optimized flavonoid leads may help generate improved anti-HCC drugs.…”

“…Flavonoids, abundant in many plant species including fruit and vegetables, are excellent leads for drug development 21 . Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound isolated from Flos Chrysanthemi Indici , has been shown to have anticancer activity against various malignancies, such as lung cancer, breast cancer and prostate cancer 22–24 , indicating its potential clinical value in cancer treatment 25 .…”

Citrus Peel as a Source of Beneficial Phytochemical and Pharmacological Potential

“…Pharmacology of citrus peels: Citrus fruits are commonly known for their uses in the field of culinary and even medical. Hesperidin, narigin, nobilentin, tangeretin, neoponcirin, narirutin and diosmin among others are common flavonoids naturally abundant in citrus [24][25][26]. In this review, common flavonoids from citrus peel are being bibliographically studied on their pharmacological potentials.…”

“…Though the natural content of 5-demethylated polymethoxyflavones in citrus peels is low, it has been confirmed that they have higher potency in combating diseases than their non-demethylated counterparts [27,28]. A number of reports have demonstrated the biological properties of these citrus flavonoids including anticarcinogenic, antidiarrheal, antihypocholesterolemic, antiobesity, antidiabetic, antioxidant and anti-inflammatory properties, which help in enhancing human health [24][25][26][27][28][29].…”