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

12 pages, 5 figures, 2 tables.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).Financial support (research grants PPQ2003-06602-C04-01 and -04, BQU2002-0485-C02-01 and doctoral fellowships to CL and ST from the Spanish Ministry of Education and Science; grant 2001SGR00048 and ITT program of the Work Community of Pyrenees from Generalitat de Catalalunya) is acknowledged. We thank Dr Irene Fernández from the Servei d'Espectrometria de Masses of the University of Barcelona for the mass spectrometry analyses, Ms Avencia Díez from the Servei d'Espectrometria de Ressonància Paramagnètica Electrònica at IIQAB-CSIC for the EPR analyses and Dr Francisco José Sánchez-Baeza and Ms Montserrat Sindreu from the Servei d'Espectrometria de Ressonància Magnètica Nuclear at IIQAB-CSIC for the NMR analyses.Peer reviewe