Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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+] ([Ca 2+]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 μM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 μM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 μM) had no effect. EGCG increased [ 3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 μM) and flufenamic acid (100 μM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca 2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 μM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]; 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.

Original languageEnglish
Pages (from-to)260-267
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume369
Issue number2
DOIs
Publication statusPublished - 2004 Feb 1

Fingerprint

Type C Phospholipases
Inositol Phosphates
Thapsigargin
Tea
Flufenamic Acid
Mefenamic Acid
epigallocatechin gallate
Lanthanum
Neomycin
Calcium-Transporting ATPases
Genistein
Astrocytoma
Polyphenols
Nifedipine
Cobalt
Indomethacin
Endoplasmic Reticulum
Protein-Tyrosine Kinases
Cardiovascular Diseases
Calcium

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kim, Hee Jung ; Yum, Keun Sang ; Sung, Jong Ho ; Rhie, Duck Joo ; Kim, Myung Jun ; Min, Do Sik ; Hahn, Sang June ; Kim, Myung Suk ; Jo, Yang Hyeok ; Yoon, Shin Hee. / Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2004 ; Vol. 369, No. 2. pp. 260-267.
@article{15b26f15072c41c799e6f26e8128decd,
title = "Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores",
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+] ([Ca 2+]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 μM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 μM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 μM) had no effect. EGCG increased [ 3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 μM) and flufenamic acid (100 μM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca 2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 μM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]; 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.",
author = "Kim, {Hee Jung} and Yum, {Keun Sang} and Sung, {Jong Ho} and Rhie, {Duck Joo} and Kim, {Myung Jun} and Min, {Do Sik} and Hahn, {Sang June} and Kim, {Myung Suk} and Jo, {Yang Hyeok} and Yoon, {Shin Hee}",
year = "2004",
month = "2",
day = "1",
doi = "10.1007/s00210-003-0852-y",
language = "English",
volume = "369",
pages = "260--267",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "2",

}

Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores. / Kim, Hee Jung; Yum, Keun Sang; Sung, Jong Ho; Rhie, Duck Joo; Kim, Myung Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung Suk; Jo, Yang Hyeok; Yoon, Shin Hee.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 369, No. 2, 01.02.2004, p. 260-267.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores

AU - Kim, Hee Jung

AU - Yum, Keun Sang

AU - Sung, Jong Ho

AU - Rhie, Duck Joo

AU - Kim, Myung Jun

AU - Min, Do Sik

AU - Hahn, Sang June

AU - Kim, Myung Suk

AU - Jo, Yang Hyeok

AU - Yoon, Shin Hee

PY - 2004/2/1

Y1 - 2004/2/1

N2 - 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+] ([Ca 2+]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 μM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 μM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 μM) had no effect. EGCG increased [ 3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 μM) and flufenamic acid (100 μM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca 2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 μM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]; 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.

AB - 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+] ([Ca 2+]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 μM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 μM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 μM) had no effect. EGCG increased [ 3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 μM) and flufenamic acid (100 μM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca 2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 μM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]; 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.

UR - http://www.scopus.com/inward/record.url?scp=10744228826&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744228826&partnerID=8YFLogxK

U2 - 10.1007/s00210-003-0852-y

DO - 10.1007/s00210-003-0852-y

M3 - Article

C2 - 14647974

AN - SCOPUS:10744228826

VL - 369

SP - 260

EP - 267

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 2

ER -