Anticancer and anti-inflammatory effects of cysteine metabolites of the green tea polyphenol, (-)-epigallocatechin-3-gallate.
(-)-Epigallocatechin-3-gallate (EGCG) has been shown to have cancer preventive activity in vitro and in vivo. We have previously shown that EGCG can undergo conjugation to cysteine to form 2'-cysteinyl-EGCG and 2''-cysteinyl-EGCG. Studies of thiol-conjugated metabolites of methamphetamine indicate that such metabolites are not detoxified but retain biological activity. Here, we examined the growth inhibitory, pro-oxidant, and anti-inflammatory activities of the cysteine metabolites of EGCG. Both compounds dose-dependently inhibited the growth of colon cancer and intestinal cell lines. Both metabolites prevented aberrant arachidonic acid release and nitric oxide production by lipopolysaccharide-stimulated RAW264.7 cells. Under cell culture conditions, 2''-cysteinyl-EGCG produced H2O2 at a faster rate than EGCG. The results of the present study show that cysteine conjugates of EGCG retain the growth inhibitory, anti-inflammatory, and pro-oxidant activities of EGCG in vitro and may play a role in disease prevention in vivo. These results remain to be confirmed in vivo.
Lambert
Joshua D
JD
Department of Food Science, The Pennsylvania State University, 332 Food Science Building, University Park, Pennsylvania 16802, USA. jdl134@psu.edu
Sang
Shengmin
S
Hong
Jungil
J
Yang
Chung S
CS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D051381:Rats; D013662:Tea / Q000737:chemistry*
C554965:2''-cysteinyl-epigallocatechin-3-gallate; C554964:2'-cysteinyl-epigallocatechin-3-gallate; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D003545:Cysteine