Effects of Flavonoids from Food and Dietary Supplements on Glial and Glioblastoma Multiforme Cells

Abstract

Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these flavonoids, their importance as components of diet and dietary supplements, their bioavailability and ability to cross the blood-brain barrier, their reported beneficial health effects, and their effects on non-malignant glial as well as glioblastoma tumor cells. The reviewed flavonoids appear to protect glial cells via reduction of oxidative stress, while some also attenuate glutamate-induced excitotoxicity and reduce neuroinflammation. Most of the reviewed flavonoids inhibit proliferation of glioblastoma cells and induce their death. Moreover, some of them inhibit pro-oncogene signaling pathways and intensify the effect of conventional anti-cancer therapies. However, most of these anti-glioblastoma effects have only been observed in vitro or in animal models. Due to limited ability of the reviewed flavonoids to access the brain, their normal dietary intake is likely insufficient to produce significant anti-cancer effects in this organ, and supplementation is needed.

Keywords: bioavailability; blood-brain barrier; catechins; dietary supplements; flavonoids; food; glial cells; glioblastoma multiforme; proanthocyanidins; quercetin.

Figure 1

(A) General structural formula of flavonols; (B) structural formula of quercetin (R = OH) and kaempferol (R = H).

Figure 2

(A) General structural formula of flavan-3-ols; (B) (+)-catechin (2R,3S), the more common of the two catechin enantiomers; (C) gallate moiety; (D) Substituents of catechin derivatives.

Figure 3

(A) Dimeric A type procyanidin (epicatechin-catechin dimer) with C-4→C-8 linkage and C-2→O→C-7 ether bond. Red numbering: epicatechin moiety; green: catechin moiety; (B) dimeric B type procyanidin (epicatechin-catechin) with C-4→C-8 linkage. Red: epicatechin moiety; green: catechin moiety; (C) dimeric B type procyanidin (epicatechin-epicatechin) with C-4→C-6 linkage; (D) dimeric B type prodelphinidin (EGC-catechin) with C-4→C-8 linkage. Red: EGC; green: catechin. Additional OH group at 5′ is marked; (E) dimeric A type propelargonidin (epiafzelechin-afzelechin) with C-4→C-8 and C-2→O→C-7 bonds. Red: epiafzelechin; green: afzelechin. Note the lack of OH groups at the both 3′ positions; (F) general structural formula of anthocyanidins.