Effect of new antioxidant cysteinyl-flavanol conjugates on skin cancer cells.
Novel catechin derivatives obtained from grape procyanidins and l-cysteine scavenge free radicals by hydrogen atom donation, rather than electron transfer, and reduce cell viability in A375 and M21 melanoma cells. In particular, 4beta-(S-cysteinyl)epicatechin 3-O-gallate has a free radical scavenging capacity as strong as that of tea (-)-epigallocatechin gallate and causes a significant S-phase cell-cycle arrest in both cell lines at doses higher than 100 microM. The other cysteinyl compounds do not affect normal cell cycle distribution. The gallate derivative also induces apoptosis in melanoma cells more strongly than the other derivatives and the parent (-)-epicatechin do. The gallate compound seems to trigger nuclear condensation and fragmentation, which is confirmed by DNA laddering. Interestingly, they do not induce apoptosis in keratinocytes (HaCaT).
Lozano
Carles
C
Department of Biochemistry and Molecular Biology, Unit associated with the CSIC, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
Torres
Josep Lluís
JL
Julià
Lluís
L
Jimenez
Aurora
A
Centelles
Josep Joan
JJ
Cascante
Marta
M
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004579:Electron Transport; D005419:Flavonoids / Q000737:chemistry; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008545:Melanoma / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D027843:Vitis / Q000737:chemistry
C503918:4-(S-cysteinyl)catechin; C503917:4-(S-cysteinyl)epicatechin 3-O-gallate; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D005419:Flavonoids; D016166:Free Radical Scavengers; C404987:flavan-3-ol; D002392:Catechin; D003545:Cysteine