Full Text:   <2021>

CLC number: Q2

On-line Access: 

Received: 2008-12-20

Revision Accepted: 2009-03-03

Crosschecked: 2009-04-28

Cited: 6

Clicked: 4252

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.6 P.411~421


Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc

Author(s):  Jun-guo YANG, Hai-ning YU, Shi-li SUN, Lan-cui ZHANG, Guo-qing HE, Undurti N. DAS, Hui RUAN, Sheng-rong SHEN

Affiliation(s):  Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310029, China; more

Corresponding email(s):   shrshen@zju.edu.cn

Key Words:  Epigallocatechin-3-gallate (EGCG), Zinc, LNCaP, Membrane fluidity

Share this article to: More |Next Article >>>

Jun-guo YANG, Hai-ning YU, Shi-li SUN, Lan-cui ZHANG, Guo-qing HE, Undurti N. DAS, Hui RUAN, Sheng-rong SHEN. Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc[J]. Journal of Zhejiang University Science B, 2009, 10(6): 411~421.

@article{title="Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc",
author="Jun-guo YANG, Hai-ning YU, Shi-li SUN, Lan-cui ZHANG, Guo-qing HE, Undurti N. DAS, Hui RUAN, Sheng-rong SHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc
%A Jun-guo YANG
%A Hai-ning YU
%A Shi-li SUN
%A Lan-cui ZHANG
%A Guo-qing HE
%A Undurti N. DAS
%A Sheng-rong SHEN
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 6
%P 411~421
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820400

T1 - Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc
A1 - Jun-guo YANG
A1 - Hai-ning YU
A1 - Shi-li SUN
A1 - Lan-cui ZHANG
A1 - Guo-qing HE
A1 - Undurti N. DAS
A1 - Hui RUAN
A1 - Sheng-rong SHEN
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 6
SP - 411
EP - 421
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820400

Objective: To evaluate effects of epigallocatechin-3-gallate (EGCG) on the viability, membrane properties, and zinc distribution, with and without the presence of Zn2+, in human prostate carcinoma LNCaP cells. Methods: We examined changes in cellular morphology and membrane fluidity of LNCaP cells, distribution of cellular zinc, and the incorporated portion of EGCG after treatments with EGCG, Zn2+, and EGCG+Zn2+. Results: We observed an alteration in cellular morphology and a decrease in membrane fluidity of LNCaP cells after treatment with EGCG or Zn2+. The proportion of EGCG incorporated into liposomes treated with the mixture of EGCG and Zn2+ at the ratio of 1:1 was 90.57%, which was significantly higher than that treated with EGCG alone (30.33%). Electron spin resonance (ESR) studies and determination of fatty acids showed that the effects of EGCG on the membrane fluidity of LNCaP were decreased by Zn2+. EGCG accelerated the accumulation of zinc in the mitochondria and cytosol as observed by atomic absorption spectrometer. Conclusion: These results show that EGCG interacted with cell membrane, decreased the membrane fluidity of LNCaP cells, and accelerated zinc accumulation in the mitochondria and cytosol, which could be the mechanism by which EGCG inhibits proliferation of LNCaP cells. In addition, high concentrations of Zn2+ could attenuate the actions elicited by EGCG.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Ahmad, N., Feyes, D.K., Nieminen, A.L., Agarwal, R., Mukhtar, H., 1997. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J. Natl. Cancer Inst., 89(24): 1881-1886.

[2] Ahmad, N., Gupta, S., Mukhtar, H., 2000. Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Arch. Biochem. Biophys., 376(2):338-346.

[3] Azam, S., Hadi, N., Khan, N.U., Hadi, S.M., 2004. Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. Toxicol. in Vitro, 18(5):555-561.

[4] Balint, E., Grimley, P.M., Gan, Y., Zoon, K.C., Aszalos, A., 2005. Plasma membrane biophysical properties linked to the antiproliferative effect of interferon-alpha. Acta Microbiol. Immunol. Hung., 52(3-4):407-432.

[5] Bettuzzi, S., Brausi, M., Rizzi, F., Castagnetti, G., Peracchia, G., Corti, A., 2006. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res., 66(2):1234-1240.

[6] Bishop, G.M., Dringen, R., Robinson, S.R., 2007. Zinc stimulates the production of toxic reactive oxygen species (ROS) and inhibits glutathione reductase in astrocytes. Free Radic. Biol. Med., 42(8):1222-1230.

[7] Chen, X., Yu, H., Shen, S., Yin, J., 2007. Role of Zn2+ in epigallocatechin gallate affecting the growth of PC-3 cells. J. Trace Elem. Med. Biol., 21(2):125-131.

[8] Chen, Y.M., Wang, M.K., Huang, P.M., 2006. Catechin transformation as influenced by aluminum. J. Agric. Food Chem., 54(1):212-218.

[9] Chen, Z.P., Schell, J.B., Ho, C.T., Chen, K.Y., 1998. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett., 129(2):173-179.

[10] Chung, L.Y., Cheung, T.C., Kong, S.K., Fung, K.P., Choy, Y.M., Chan, Z.Y., Kwok, T.T., 2001. Induction of apoptosis by green tea catechins in human prostate cancer DU145 cells. Life Sci., 68(10):1207-1214.

[11] Cooper, R.A., 1977. Abnormalities of cell-membrane fluidity in the pathogenesis of disease. N. Engl. J. Med., 297(7): 371-377.

[12] Costello, L.C., Franklin, R.B., Feng, P., 2005. Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer. Mitochondrion, 5(3):143-153.

[13] de Gómez Dumm, N.T., Giammona, A.M., Touceda, L.A., Raimondi, C., 2001. Lipid abnormalities in chronic renal failure patients undergoing hemodialysis. Medicina (B Aires), 61(2):142-146.

[14] Esparza, I., Salinas, I., Santamara, C., Garcia-Mina, J.M., Fernandez, J.M., 2005. Electrochemical and theoretical complexation studies for Zn and Cu with individual polyphenols. Anal. Chim. Acta, 543(1-2):267-274.

[15] Feng, P., Liang, J.Y., Li, T.L., Guan, Z.X., Zou, J., Franklin, R., Costello, L.C., 2000. Zinc induces mitochondria apoptogenesis in prostate cells. Mol. Urol., 4(1):31-36.

[16] Feng, P., Li, T.L., Guan, Z.X., Franklin, R.B., Costello, L.C., 2002. Direct effect of zinc on mitochondrial apoptogenesis in prostate cells. Prostate, 52(4):311-318.

[17] Feng, P., Li, T.L., Guan, Z.X., Franklin, R.B., Costello, L.C., 2003. Effect of zinc on prostatic tumorigenicity in nude mice. Ann. N. Y. Acad. Sci., 1010(1-2):316-320.

[18] Franklin, R.B., Costello, L.C., 2007. Zinc as an anti-tumor agent in prostate cancer and in other cancers. Arch. Biochem. Biophys., 463(2):211-217.

[19] Fujimura, Y., Yamada, K., Tachibana, H., 2005. A lipid raft-associated 67 kDa laminin receptor mediates suppressive effect of epigallocatechin-3-O-gallate on FcepsilonRI expression. Biochem. Biophys. Res. Commun., 336(2):674-681.

[20] Furukawa, A., Oikawa, S., Murata, M., Hiraku, Y., Kawanishi, S., 2003. (−)-Epigallocatechin gallate causes oxidative damage to isolated and cellular DNA. Biochem. Pharmacol., 66(9):1769-1778.

[21] Gallus, S., Foschi, R., Negri, E., Talamini, R., Franceschi, S., Montella, M., Ramazzotti, V., Tavani, A., Dal Maso, L., La Vecchia, C., 2007. Dietary zinc and prostate cancer risk: a case-control study from Italy. Eur. Urol., 52(4): 1052-1056.

[22] Gupta, S., Ahmad, N., Nieminen, A.L., Mukhtar, H., 2000. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (−)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol. Appl. Pharmacol., 164(1):82-90.

[23] Hashimoto, T., Kumazawa, S., Nanjo, F., Hara, Y., Nakayama, T., 1999. Interaction of tea catechins with lipid bilayers investigated with liposome systems. Biosci. Biotechnol. Biochem., 63(12):2252-2255.

[24] Hayakawa, F., Ishizu, Y., Hoshino, N., Yamaji, A., Ando, T., Kimura, T., 2004. Prooxidative activities of tea catechins in the presence of Cu2+. Biosci. Biotechnol. Biochem., 68(9):1825-1830.

[25] Kagaya, N., Kawase, M., Maeda, H., Tagawa, Y., Nagashima, H., Ohmori, H., Yagi, K., 2002. Enhancing effect of zinc on hepatoprotectivity of epigallocatechin gallate in isolated rat hepatocytes. Biol. Pharm. Bull., 25(9): 1156-1160.

[26] Kajiya, K., Kumazawa, S., Nakayama, T., 2001. Steric effects on interaction of tea catechins with lipid bilayers. Biosci. Biotechnol. Biochem., 65(12):2638-2643.

[27] Kampa, M., Papakonstanti, E.A., Hatzoglou, A., Stathopoulos, E.N., Stournaras, C., Castanas, E., 2002. The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. FASEB J., 16(11): 1429-1431.

[28] Kampa, M., Nifli, A.P., Charalampopoulos, I., Alexaki, V.I., Theodoropoulos, P.A., Stathopoulos, E.N., Gravanis, A., Castanas, E., 2005. Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp. Cell Res., 307(1):41-51.

[29] Kanadzu, M., Lu, Y., Morimoto, K., 2006. Dual function of (−)-epigallocatechin gallate (EGCG) in healthy human lymphocytes. Cancer Lett., 241(2):250-255.

[30] Knapp, D.R., 1979. Handbook of Analytical Derivatization Reactions. Wiley Publishers, New York, USA, p.164.

[31] Liang, J.Y., Liu, Y.Y., Zou, J., Franklin, R.B., Costello, L.C., Feng, P., 1999. Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate, 40(3):200-207.

[32] Liao, S., Umekita, Y., Guo, J., Kokontis, J.M., Hiipakka, R.A., 1995. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett., 96(2):239-243.

[33] Navarro, R.E., Santacruz, H., Inoue, M., 2005. Complexation of epigallocatechin gallate (a green tea extract, EGCG) with Mn2+: nuclear spin relaxation by the paramagnetic ion. J. Inorg. Biochem., 99(2):584-588.

[34] Nodera, M., Yanagisawa, H., Wada, O., 2001. Increased apoptosis in a variety of tissues of zinc-deficient rats. Life Sci., 69(14):1639-1649.

[35] Oikawa, S., Furukawaa, A., Asada, H., Hirakawa, K., Kawanishi, S., 2003. Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species. Free Radic. Res., 37(8):881-890.

[36] Reznichenko, L., Amit, T., Zheng, H., Avramovich-Tirosh, Y., Youdim, M.B., Weinreb, O., Mandel, S., 2006. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (−)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer’s disease. J. Neurochem., 97(2):527-536.

[37] Salinas, D.G., De La Fuente, M., Reyes, J.G., 2005. Changes of enzyme activity in lipid signaling pathways related to substrate reordering. Biophys. J., 89(2):885-894.

[38] Singh, K.K., Desouki, M.M., Franklin, R.B., Costello, L.C., 2006. Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues. Mol. Cancer, 5(1):14.

[39] Stathopoulos, E.N., Dambaki, C., Kampa, M., Theodoropoulos, P.A., Anezinis, P., Delakas, D., Delides, G.S., Castanas, E., 2003. Membrane androgen binding sites are preferentially expressed in human prostate carcinoma cells. BMC Clin. Pathol., 3(1):1.

[40] Sunshine, C., McNamee, M.G., 1994. Lipid modulation of nicotinic acetylcholine receptor function: the role of membrane lipid composition and fluidity. Biochim. Biophys. Acta, 1191(1):59-64.

[41] Tachibana, H., Koga, K., Fujimura, Y., Yamada, K., 2004. A receptor for green tea polyphenol EGCG. Nat. Struct. Mol. Biol., 11(4):380-381.

[42] Teresa, G., Anna, A., Maria, P., Zofia, J., Gerard, B., 2002. Carp erythrocyte lipids as a potential target for the toxic action of zinc ions. Toxicol. Lett., 132(1):57-64.

[43] Thewke, D., Kramer, M., Sinensky, M.S., 2000. Transcriptional homeostatic control of membrane lipid composition. Biochem. Biophys. Res. Commun., 273(1):1-4.

[44] Truong-Tran, A.Q., Ho, L.H., Chai, F., Zalewski, P.D., 2000. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J. Nutr., 130(5S): 1459S-1466S.

[45] Tsui, K.H., Chang, P.L., Juang, H.H., 2006. Zinc blocks gene expression of mitochondrial aconitase in human prostatic carcinoma cells. Int. J. Cancer, 118(3):609-615.

[46] Turk, M., Méjanelle, L., Sentjurc, M., Grimalt, J.O., Gunde-Cimerman, N., Plemenitas, A., 2004. Salt-induced changes in lipid composition and membrane fluidity of halophilic yeast-like melanized fungi. Extremophiles, 8(1):53-61.

[47] Uzzo, R.G., Crispen, P.L., Golovine, K., Makhov, P., Horwitz, E.M., Kolenko, V.M., 2006. Diverse effects of zinc on NF-kappaB and AP-1 transcription factors: implications for prostate cancer progression. Carcinogenesis, 27(10): 1980-1990.

[48] Vayalil, P.K., Katiyar, S.K., 2004. Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells. Prostate, 59(1):33-42.

[49] Yaman, M., Atici, D., Bakirdere, S., Akdeniz, I., 2005. Comparison of trace metal concentrations in malign and benign human prostate. J. Med. Chem., 48(2):630-634.

[50] Yu, H.N., Shen, S.R., Xiong, Y.K., 2005. Cytotoxicity of epigallocatechin-3-gallate to LNCaP cells in the presence of Cu2+. J. Zhejiang Univ. Sci. B, 6(2):125-131.

[51] Yu, H.N., Shen, S.R., Yin, J.J., 2007. Effects of interactions of EGCG and Cd(2+) on the growth of PC-3 cells and their mechanisms. Food Chem. Toxicol., 45(2):244-249.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE