Electron‐transfer capacity of catechin derivatives and influence on the cell cycle and apoptosis in HT29 cells

Abstract

Galloylated and nongalloylated catechin conjugates with cysteine derivatives have been synthesized and evaluated for their capacity to scavenge free radicals and to influence crucial functions (cell cycle, apoptosis) in HT29 colon carcinoma cells. We show that the nonphenolic part of the molecule modified the capacity of catechins to donate hydrogen atoms and to transfer electrons to free radicals. Nongalloylated derivatives did not significantly influence either the cell cycle or apoptosis. Among the galloylated species, 4β‐[S‐(O‐ethyl‐cysteinyl)]epicatechin 3‐O‐gallate, which showed a high electron‐transfer capacity (5 e– per molecule), arrested the cell cycle and induced apoptosis as expected for galloylated catechins such as tea (–)‐epigallocatechin 3‐O‐gallate. 4β‐[S‐(N‐Acetyl‐O‐methyl‐cysteinyl)]epicatechin 3‐O‐gallate, which showed the highest hydrogen‐donating capacity (10 H per molecule) while keeping the electron‐transfer capacity low (2.9 e– per molecule), did not trigger any significant apoptosis. The gallate moiety did not appear to be sufficient for the pro‐apoptotic effect of the catechin derivatives in HT29 cells. Instead, a high electron‐transfer capacity is more likely to be behind this effect. The use of stable radicals sensitive exclusively to electron transfer may help to design molecules with either preventive scavenging action (high hydrogen donation, low electron transfer) or therapeutic pro‐apoptotic activity (high electron transfer).

Absorption and Metabolization of Cytoprotective Epicatechin Thio Conjugates in Rats

“…We have reported that conjugates of catechins with thiol-containing molecules such as cysteine and cysteamine share with other polyphenols their putatively beneficial antioxidant properties that are mainly attributed to the catechol or pyrogallol groups (Torres and Bobet, 2001;Lozano et al, 2006). We have also shown that the nonphenolic part of the molecule contributes significantly to the overall antioxidant effect.…”

Hybrid‐Increased Radical‐Scavenging Activity of Resveratrol Derivatives by Incorporating a Chroman Moiety of Vitamin E

“…[13] By use of this radical, an intriguing observation that the electron-transfer capacity of catechin derivatives correlates well with cell-cycle-arrest activity and apoptosis-inducing activity in HT29 cells, was obtained. [14] Thus, HNTTMC was selected to evaluate the radicalscavenging property of hydroxylated stilbene-chroman hybrids (11 a-11 c) and their corresponding parent molecules resveratrol and PMC. When 11 b was added to the chloroform/methanol solution, the rapid disappearance of the visible absorption band of HNTTMC centered at 387 nm was accompanied by the appearance of a peak at 497 nm due to the formation of the corresponding anion HNTTM À (Figure 1), [13] indicating that the electron-transfer reaction from 11 b to HNTTMC took place.…”

Grape Epicatechin Conjugates Prevent Erythrocyte Membrane Protein Oxidation

“…Conjugates were prepared by acidic depolymerisation of proanthocyanidins obtained from grape (Vitis Vinifera) pomace and from hazel (Hamamelis virginiana) bark, essentially as described inTorres and Bobet (2001) (5) andLozano et al (2006) (10). We aimed to generate bio-based antioxidants with modified physicochemical and biological properties.…”