Antioxidants regulate normal human keratinocyte differentiation.
Cancer begins with a normal cell that, due to persistent environmental insult, is transformed, via a series of progressively more insidious steps, into a cancer cell. A major goal of chemopreventive therapy is to alter the normal cell response to the environmental agent with the goal of inhibiting disease progression. (-)-Epigallocatechin-3-gallate (EGCG) is an important bioactive green tea antioxidant that possesses remarkable cancer chemopreventive properties. We have recently explored the hypothesis that EGCG prevents cancer by promoting keratinocyte differentiation. Based on our findings, we argue that EGCG acts to enhance the differentiation of normal keratinocytes. This is a potentially important finding, as it represents a novel mechanism of disease inhibition by EGCG--cancer preventive "differentiation therapy". However, not all antioxidant chemopreventive agents work by this mechanism. Curcumin, for example, inhibits the differentiation-promoting activity of EGCG. This report discusses the mechanism of EGCG and curcumin action in regulating expression of involucrin, a marker of keratinocyte differentiation.
Eckert
Richard L
RL
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106-4970, USA. rle2@po.cwru.edu
Crish
James F
JF
Efimova
Tatiana
T
Balasubramanian
Sivaprakasam
S
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D048292:Mitogen-Activated Protein Kinase 13; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D013662:Tea / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases
D016588:Anticarcinogenic Agents; D022762:CCAAT-Enhancer-Binding Proteins; D011498:Protein Precursors; D013662:Tea; C032253:involucrin; D002392:Catechin; C045651:epigallocatechin gallate; D048292:Mitogen-Activated Protein Kinase 13; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin