Abstract |
Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]- inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+- ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]- inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.
|
Authors | Hee Jung Kim, Keun Sang Yum, Jong-Ho Sung, Duck-Joo Rhie, Myung-Jun Kim, Do Sik Min, Sang June Hahn, Myung-Suk Kim, Yang-Hyeok Jo, Shin Hee Yoon |
Journal | Naunyn-Schmiedeberg's archives of pharmacology
(Naunyn Schmiedebergs Arch Pharmacol)
Vol. 369
Issue 2
Pg. 260-7
(Feb 2004)
ISSN: 0028-1298 [Print] Germany |
PMID | 14647974
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Inositol Phosphates
- Ion Channels
- Tea
- ortho-Aminobenzoates
- Mefenamic Acid
- Flufenamic Acid
- Catechin
- fenamic acid
- epigallocatechin gallate
- Genistein
- Protein-Tyrosine Kinases
- Type C Phospholipases
- Calcium
|
Topics |
- Calcium
(metabolism)
- Catechin
(analogs & derivatives, pharmacology)
- Enzyme Activation
- Flufenamic Acid
(chemistry, pharmacology)
- Genistein
(pharmacology)
- Inositol Phosphates
(biosynthesis)
- Ion Channels
(antagonists & inhibitors)
- Mefenamic Acid
(chemistry, pharmacology)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Tea
(chemistry)
- Tumor Cells, Cultured
- Type C Phospholipases
(antagonists & inhibitors, metabolism)
- ortho-Aminobenzoates
(chemistry)
|