Opposing action of curcumin and green tea polyphenol in human keratinocytes.
Persistent environmental insult can convert a normal cell into a cancer cell. However, various natural chemopreventive agents called antioxidants can retard this progression. We have recently explored the effects of several chemopreventive agents, including green tea polyphenol and curcumin, on normal human keratinocyte function. Our findings suggest that a bioactive polyphenol from green tea, (-)-epigallocatechin-3-gallate (EGCG), acts to increase involucrin gene expression, suggesting that EGCG treatment enhances normal human keratinocyte differentiation. Mechanistic studies indicate that EGCG alters mitogen-activated protein kinase cascade function to activate involucrin gene transcription via a Ras, MEKK1, MEK3, ERK1/2-p38delta cascade that targets AP1 and CAATT enhancer binding protein transcription factors. These findings suggest that EGCG may inhibit disease progression by promoting keratinocyte differentiation. Parallel studies indicate that not all antioxidants produce a similar response. Curcumin, an antioxidant derived from the turmeric, antagonizes the EGCG-dependent response by interfering in this signaling pathway. These studies suggest that different antioxidant may produce antagonistic effects in tissues.
Eckert
Richard L
RL
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA. rle2@po.cwru.edu
Crish
James F
JF
Efimova
Tatiana
T
Balasubramanian
Sivaprakasam
S
D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018890:Chemoprevention; D003474:Curcumin / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D011498:Protein Precursors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D011498:Protein Precursors; D013662:Tea; C032253:involucrin; D002392:Catechin; C045651:epigallocatechin gallate; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin