Anticancer and Anti-inflammatory Effects of Cysteine Metabolites of the Green Tea Polyphenol, (-)-epigallocatechin-3-gallate

Overview

Journal J Agric Food Chem

Specialties Chemistry
Nutritional Sciences

Date 2010 Aug 20

PMID 20718469

Citations 15

Authors

Joshua D Lambert

Shengmin Sang

Jungil Hong

Chung S Yang

Affiliations

Soon will be listed here.

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) has been shown to have cancer preventive activity in vitro and in vivo. We have previously shown that EGCG can undergo conjugation to cysteine to form 2'-cysteinyl-EGCG and 2''-cysteinyl-EGCG. Studies of thiol-conjugated metabolites of methamphetamine indicate that such metabolites are not detoxified but retain biological activity. Here, we examined the growth inhibitory, pro-oxidant, and anti-inflammatory activities of the cysteine metabolites of EGCG. Both compounds dose-dependently inhibited the growth of colon cancer and intestinal cell lines. Both metabolites prevented aberrant arachidonic acid release and nitric oxide production by lipopolysaccharide-stimulated RAW264.7 cells. Under cell culture conditions, 2''-cysteinyl-EGCG produced H2O2 at a faster rate than EGCG. The results of the present study show that cysteine conjugates of EGCG retain the growth inhibitory, anti-inflammatory, and pro-oxidant activities of EGCG in vitro and may play a role in disease prevention in vivo. These results remain to be confirmed in vivo.

Citing Articles

Natural Rubber/Hexagonal Mesoporous Silica Nanocomposites as Efficient Adsorbents for the Selective Adsorption of (-)-Epigallocatechin Gallate and Caffeine from Green Tea.

Jermjun K, Khumho R, Thongoiam M, Yousatit S, Yokoi T, Ngamcharussrivichai C Molecules. 2023; 28(16).

PMID: 37630270 PMC: 10458317. DOI: 10.3390/molecules28166019.

Mechanism of (-)-epigallocatechin gallate (EGCG) dimerization by low-temperature plasma.

Park S, Jeong G, Jee S, Kim T, Kim S Sci Rep. 2022; 12(1):15396.

PMID: 36100688 PMC: 9470551. DOI: 10.1038/s41598-022-19806-0.

FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells.

Pham D, Chang Y, Lin S, Fuh Y, Tsai M, Weng C Molecules. 2018; 23(12).

PMID: 30486505 PMC: 6321370. DOI: 10.3390/molecules23123110.

Bioinformatic Prediction of Possible Targets and Mechanisms of Action of the Green Tea Compound Epigallocatechin-3-Gallate Against Breast Cancer.

Song X, Zhang M, Chen L, Lin Q Front Mol Biosci. 2017; 4:43.

PMID: 28713815 PMC: 5492114. DOI: 10.3389/fmolb.2017.00043.

Anti‑proliferative activity of epigallocatechin‑3‑gallate and silibinin on soft tissue sarcoma cells.

Harati K, Behr B, Wallner C, Daigeler A, Hirsch T, Jacobsen F Mol Med Rep. 2016; 15(1):103-110.

PMID: 27909727 PMC: 5355719. DOI: 10.3892/mmr.2016.5969.

References

Hong J, Lu H, Meng X, Ryu J, Hara Y, Yang C . Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (-)-epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells. Cancer Res. 2002; 62(24):7241-6. View

Bai F, Lau S, Monks T . Glutathione and N-acetylcysteine conjugates of alpha-methyldopamine produce serotonergic neurotoxicity: possible role in methylenedioxyamphetamine-mediated neurotoxicity. Chem Res Toxicol. 1999; 12(12):1150-7. DOI: 10.1021/tx990084t. View

Ryu J, Ahn H, Lee H . Inhibition of nitric oxide production on LPS-activated macrophages by kazinol B from Broussonetia kazinoki. Fitoterapia. 2003; 74(4):350-4. DOI: 10.1016/s0367-326x(03)00062-5. View

Landis-Piwowar K, Wan S, Wiegand R, Kuhn D, Chan T, Dou Q . Methylation suppresses the proteasome-inhibitory function of green tea polyphenols. J Cell Physiol. 2007; 213(1):252-60. DOI: 10.1002/jcp.21124. View

Dou Q . Molecular mechanisms of green tea polyphenols. Nutr Cancer. 2010; 61(6):827-35. PMC: 3769684. DOI: 10.1080/01635580903285049. View

Lambert J, Sang S, Yang C . Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol Pharm. 2007; 4(6):819-25. DOI: 10.1021/mp700075m. View

Fang M, Wang Y, Ai N, Hou Z, Sun Y, Lu H . Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003; 63(22):7563-70. View

Li G, Chen Y, Hou Z, Xiao H, Jin H, Lu G . Pro-oxidative activities and dose-response relationship of (-)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: a comparative study in vivo and in vitro. Carcinogenesis. 2010; 31(5):902-10. PMC: 2864413. DOI: 10.1093/carcin/bgq039. View

Yang C, Wang X, Lu G, Picinich S . Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009; 9(6):429-39. PMC: 2829848. DOI: 10.1038/nrc2641. View

10.

Lambert J, Rice J, Hong J, Hou Z, Yang C . Synthesis and biological activity of the tea catechin metabolites, M4 and M6 and their methoxy-derivatives. Bioorg Med Chem Lett. 2005; 15(4):873-6. DOI: 10.1016/j.bmcl.2004.12.070. View

11.

Sang S, Lambert J, Hong J, Tian S, Lee M, Stark R . Synthesis and structure identification of thiol conjugates of (-)-epigallocatechin gallate and their urinary levels in mice. Chem Res Toxicol. 2005; 18(11):1762-9. DOI: 10.1021/tx050151l. View

12.

Bold R, Virudachalam S, McConkey D . Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. J Surg Res. 2001; 100(1):11-7. DOI: 10.1006/jsre.2001.6194. View

13.

Lambert J, Kennett M, Sang S, Reuhl K, Ju J, Yang C . Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Food Chem Toxicol. 2009; 48(1):409-16. PMC: 2905152. DOI: 10.1016/j.fct.2009.10.030. View

14.

Bode A, Dong Z . Epigallocatechin 3-gallate and green tea catechins: United they work, divided they fail. Cancer Prev Res (Phila). 2009; 2(6):514-7. PMC: 2822459. DOI: 10.1158/1940-6207.CAPR-09-0083. View

15.

Monks T, Jones D, Bai F, Lau S . The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity. Ther Drug Monit. 2004; 26(2):132-6. DOI: 10.1097/00007691-200404000-00008. View

16.

Lu H, Meng X, Li C, Sang S, Patten C, Sheng S . Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab Dispos. 2003; 31(4):452-61. DOI: 10.1124/dmd.31.4.452. View

17.

Elbling L, Weiss R, Teufelhofer O, Uhl M, Knasmueller S, Schulte-Hermann R . Green tea extract and (-)-epigallocatechin-3-gallate, the major tea catechin, exert oxidant but lack antioxidant activities. FASEB J. 2005; 19(7):807-9. DOI: 10.1096/fj.04-2915fje. View

18.

Lambert J, Kwon S, Hong J, Yang C . Salivary hydrogen peroxide produced by holding or chewing green tea in the oral cavity. Free Radic Res. 2007; 41(7):850-3. DOI: 10.1080/10715760601091659. View

19.

Lambert J, Sang S, Hong J, Kwon S, Lee M, Ho C . Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate. Drug Metab Dispos. 2006; 34(12):2111-6. DOI: 10.1124/dmd.106.011460. View

20.

Chen D, Wang C, Lambert J, Ai N, Welsh W, Yang C . Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies. Biochem Pharmacol. 2005; 69(10):1523-31. DOI: 10.1016/j.bcp.2005.01.024. View