Editors' ChoiceANTIOXIDANTS

Mixing Turmeric and Tea

STKE  08 Jun 2004:
Vol. 2004, Issue 236, pp. tw205
DOI: 10.1126/stke.2362004tw205

Antioxidants from natural sources have been viewed as protective against many diseases. However, it is unclear whether different antioxidants have the same effects in any particular cellular scenario. Using involucrin expression as a marker of differentiation, Balasubramanian and Eckert compared the effects of EGCG [(–) epigallocatechin-3-gallate, a polyphenol from green tea] with those of curcumin (diferuloylmethane or turmeric, a polyphenol from Curcuma longa), two plant-derived antioxidants reported to inhibit skin cancer. EGCG stimulated transcription of a gene reporter containing the human involucrin (hINV) promoter and increased the amount of involucrin in human keratinocytes. Mutational analysis indicated that this activation depended on a C/EBP (CCAAT/enhancer-binding protein) site. C/EBPα, β, and γ expression vectors also stimulated hINV transcription, and EGCG treatment increased C/EBPα and C/EBPβ in keratinocyte nuclear extracts and C/EBP binding to the hINV C/EBP site. Curcumin did not itself increase hINV transcriptional activity, and it antagonized the effects of EGCG. Having previously shown that EGCG activates hINV expression through a Ras-MEKK1 (mitogen-activated protein kinase kinase kinase 1)-MEK3 (mitogen-activated protein kinase kinase 3)-p38δ signaling cascade, the authors transfected cells with MEKK1 or with activated Ras and found that curcumin inhibited their activation of the hINV reporter, which indicated that it acts downstream of MEKK1. Curcumin inhibited not only the EGCG-dependent increase in C/EBP but also an increase due to C/EBP overexpression; pharmacological analysis suggested that this reduction in C/EBP depended on proteasome activity. Thus, the specific effects of different natural antioxidants may vary and combining multiple antioxidants may lead to unanticipated results.

S. Balasubramanian, R. L. Eckert, Green tea polyphenol and curcumin inversely regulate human involucrin promoter activity via opposing effects on CCAAT/enhancer-binding protein function. J. Biol. Chem. 279, 24007-24014 (2004). [Abstract] [Full Text]