(-)-Epigallocatechin-3-gallate in Camellia sinensis leaves from Himalayan region of Sikkim: inhibitory effects against biochemical events and tumor initiation in Sencar mouse skin.
Recently, we and others showed that the components of green tea may be useful cancer chemopreventive agents. It has been suggested that (-)-epigallocatechin-3-gallate (EGCG), the major constituent in green tea, may possess antitumor-promoting and/or anticarcinogenic effects in rodent tumor bioassay systems. During the chemical analysis of various green tea products, we found a traditionally preserved preparation of green tea used by tribes in the Himalayan region of Sikkim, India that was rich in EGCG. EGCG was isolated from this tea product, and its inhibitory effects were evaluated against the binding of topically applied 3H-labeled polycyclic aromatic hydrocarbons (PAHs) to epidermal DNA and 12-O-tetradecanoylphorbol-13-acetate (TPA) caused induction of epidermal ornithine decarboxylase (ODC) activity in Sencar mice, the short-term markers of tumor initiation and tumor promotion, respectively. Preapplication of EGCG resulted in significant inhibition (p less than 0.05) in the binding of [3H]PAH to epidermal DNA. Similarly, the topical application of EGCG resulted in significant inhibition (p less than 0.005) in TPA-caused induction of epidermal ODC activity. In further studies, we assessed the anti-skin tumor-initiating effect of EGCG in Sencar mice in an initiation-promotion protocol. The application of EGCG before challenge with 7,12-dimethylbenz[a]anthracene as tumor initiator resulted in significant reduction both in percentage of mice with tumors and number of tumors per mouse compared with a non-EGCG-pretreated group of animals. The results of the present study suggest that the green tea preparation from Sikkim may be a good source for the isolation of EGCG and that this compound may have significant potential as a cancer chemopreventive agent.
Katiyar
S K
SK
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH.
Agarwal
R
R
Wang
Z Y
ZY
Bhatia
A K
AK
Mukhtar
H
H
D000279:Administration, Cutaneous; D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D009637:Masoprocol / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D012819:Sikkim; D012878:Skin Neoplasms / Q000517:prevention & control*; D013662:Tea / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate; D014316:Tritium
D016587:Antimutagenic Agents; D013662:Tea; D014316:Tritium; D009637:Masoprocol; D002392:Catechin; D004247:DNA; C045651:epigallocatechin gallate; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate