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Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice

Published:January 14, 2010DOI:https://doi.org/10.1016/j.ajog.2009.10.885

      Objective

      The purpose of this study was to investigate the effect of epigallocatechin gallate (EGCG) on rat leiomyoma (ELT3) cells in vitro and in a nude mice model.

      Study Design

      ELT3 cells were treated with various concentrations of EGCG. Cell proliferation, proliferation cell nuclear antigen (PCNA), and cyclin-dependent kinase 4 (Cdk4) protein levels were evaluated. ELT3 cells were inoculated subcutaneously in female athymic nude mice. Animals were fed 1.25 mg EGCG (in drinking water)/mouse/day. Tumors were collected and evaluated at 4 and 8 weeks after the treatment.

      Results

      Inhibitory effect of EGCG (200 μmol/L) on ELT3 cells was observed after 24 hours of treatment (P < .05). At ≥50 μmol/L, EGCG significantly decreased PCNA and Cdk4 protein levels (P < .05). In vivo, EGCG treatment dramatically reduced the volume and weight of tumors at 4 and 8 weeks after the treatment (P < .05). The PCNA and Cdk4 protein levels were significantly reduced in the EGCG-treated group (P < .05).

      Conclusion

      EGCG effectively inhibits proliferation and induces apoptosis in rat ELT3 uterine leiomyoma cells in vitro and in vivo.

      Key words

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      References

        • Graham H.N.
        Green tea composition, consumption, and polyphenol chemistry.
        Prev Med. 1992; 21: 334-350
        • Aggarwal B.B.
        • Shishodia S.
        Molecular targets of dietary agents for prevention and therapy of cancer.
        Biochem Pharmacol. 2006; 71: 1397-1421
        • Imai K.
        • Suga K.
        • Nakachi K.
        Cancer-preventive effects of drinking green tea among a Japanese population.
        Prev Med. 1997; 26: 769-775
        • Caltagirone S.
        • Rossi C.
        • Poggi A.
        • et al.
        Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.
        Int J Cancer. 2000; 87: 595-600
        • Waladkhani A.R.
        • Clemens M.R.
        Effect of dietary phytochemicals on cancer development.
        Int J Mol Med. 1998; 1: 747-753
        • Gao Y.T.
        • McLaughlin J.K.
        • Blot W.J.
        • Ji B.T.
        • Dai Q.
        • Fraumeni Jr, J.F.
        Reduced risk of esophageal cancer associated with green tea consumption.
        J Natl Cancer Inst. 1994; 86: 855-858
        • Ji B.T.
        • Chow W.H.
        • Hsing A.W.
        • et al.
        Green tea consumption and the risk of pancreatic and colorectal cancers.
        Int J Cancer. 1997; 70: 255-258
        • Suganuma M.
        • Okabe S.
        • Sueoka N.
        • et al.
        Green tea and cancer chemoprevention.
        Mutat Res. 1999; 428: 339-344
        • Stewart E.A.
        Uterine fibroids.
        Lancet. 2001; 357: 293-298
        • Cramer S.F.
        • Patel A.
        The frequency of uterine leiomyomas.
        Am J Clin Pathol. 1990; 94: 435-438
        • Parker W.H.
        Uterine myomas: management.
        Fertil Steril. 2007; 88: 255-271
        • Salama S.A.
        • Kamel M.
        • Christman G.
        • Wang H.Q.
        • Fouad H.M.
        • Al-Hendy A.
        Gene therapy of uterine leiomyoma: adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir treatment inhibits growth of human and rat leiomyoma cells in vitro and in a nude mouse model.
        Gynecol Obstet Invest. 2007; 63: 61-70
        • Al-Hendy A.
        • Salama S.
        Gene therapy and uterine leiomyoma: a review.
        Hum Reprod Update. 2006; 12: 385-400
        • Syed D.N.
        • Khan N.
        • Afaq F.
        • Mukhtar H.
        Chemoprevention of prostate cancer through dietary agents: progress and promise.
        Cancer Epidemiol Biomarkers Prev. 2007; 16: 2193-2203
        • Mukhtar H.
        • Ahmad N.
        Green tea in chemoprevention of cancer.
        Toxicol Sci. 1999; 52: 111-117
        • Bonovas S.
        • Tsantes A.
        • Drosos T.
        • Sitaras N.M.
        Cancer chemoprevention: a summary of the current evidence.
        Anticancer Res. 2008; 28: 1857-1866
        • Howe S.R.
        • Gottardis M.M.
        • Everitt J.I.
        • Goldsworthy T.L.
        • Wolf D.C.
        • Walker C.
        Rodent model of reproductive tract leiomyomata: establishment and characterization of tumor-derived cell lines.
        Am J Pathol. 1995; 146: 1568-1579
        • Azab S.S.
        • Salama S.A.
        • Abdel-Naim A.B.
        • Khalifa A.E.
        • El-Demerdash E.
        • Al-Hendy A.
        2-Methoxyestradiol and multidrug resistance: can 2-methoxyestradiol chemosensitize resistant breast cancer cells?.
        Breast Cancer Res Treat. 2009; 113: 9-19
        • Salama S.A.
        • Nasr A.B.
        • Dubey R.Z.K.
        • Al-Hendy A.
        Estrogen metabolite 2-methoxyestradiol induces apoptosis and inhibits cell proliferation and collagen production in rat and human leiomyoma cells: a potential medicinal treatment for uterine fibroids.
        J Soc Gynecol Investig. 2006; 13: 542-550
        • Liang Y.C.
        • Lin-Shiau S.Y.
        • Chen C.F.
        • Lin J.K.
        Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3-gallate.
        J Cell Biochem. 1999; 75: 1-12
        • Ahmad N.
        • Feyes D.K.
        • Nieminen A.L.
        • Agarwal R.
        • Mukhtar H.
        Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells.
        J Natl Cancer Inst (Bethesda). 1997; 89: 1881-1886
        • Gupta S.
        • Ahmad N.
        • Nieminen A.L.
        • Mukhtar H.
        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. 2000; 164: 82-90
        • Tang Y.
        • Zhao D.Y.
        • Elliott S.
        • et al.
        Epigallocatechin-3 gallate induces growth inhibition and apoptosis in human breast cancer cells through survivin suppression.
        Int J Oncol. 2007; 31: 705-711
        • Naasani I.
        • Oh-Hashi F.
        • Oh-Hara T.
        • et al.
        Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo.
        Cancer Res. 2003; 63: 824-830
        • Garbisa S.
        • Biggin S.
        • Cavallarin N.
        • Sartor L.
        • Benelli R.
        • Albini A.
        Tumor invasion: molecular shears blunted by green tea [letter].
        Nat Med. 1999; 5: 1216
        • Demeule M.
        • Brossard M.
        • Page M.
        • Gingras D.
        • Beliveau R.
        Matrix metalloproteinase inhibition by green tea catechins.
        Biochim Biophys Acta. 2000; 1478: 51-60
        • Jung Y.D.
        • Kim M.S.
        • Shin B.A.
        • et al.
        EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells.
        Br J Cancer. 2001; 84: 844-850
        • Masuda M.
        • Suzui M.
        • Weinstein I.B.
        Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression and chemosensitivity in human head and neck squamous cell carcinoma cell lines.
        Clin Cancer Res. 2001; 7: 4220-4229
        • Khan N.
        • Afaq F.
        • Saleem M.
        • Ahmad N.
        • Mukhtar H.
        Targeting multiple signaling pathways by green tea polyphenol (–)-epigallocatechin-3-gallate.
        Cancer Res. 2006; 66: 2500-2505
        • Al-Hendy A.
        • Salama S.A.
        Catechol-O-methyltransferase polymorphism is associated with increased uterine leiomyoma risk in different ethnic groups.
        J Soc Gynecol Invest. 2006; 13: 136-144
        • Salama S.A.
        • Ho S.
        • Wang H.Q.
        • Tenhunen J.
        • Tilgmann C.
        • Al-Hendy A.
        Hormonal regulation of catechol-O-methyl transferase activity in women with uterine leiomyomas.
        Fertil Steril. 2006; 86: 259-262
        • Othman E.
        • Al-Hendy A.
        Molecular genetics racial disparities of uterine leiomyomas.
        Best Pract Res Clin Obstet Gynecol. 2008; 22: 589-601
        • Chen D.
        • Wang C.Y.
        • Lambert J.D.
        • Ai N.
        • Welsh W.J.
        • Yang C.S.
        Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies.
        Biochem Pharmacol. 2005; 69: 1523-1531
        • Zhu B.T.
        • Shim J.Y.
        • Nagai M.
        • Bai H.W.
        Molecular modeling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (–)-epigallocatechin-3-O-gallate.
        Xenobiotica. 2008; 38: 130-146
        • Lu H.
        • Meng X.
        • Yang C.S.
        Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (–)-epigallocatechin gallate.
        Drug Metab Dispos. 2003; 31: 572-579
        • Lee M.J.
        • Maliakal P.
        • Chen L.
        • et al.
        Pharmacokinetics of tea catechins after ingestion of green tea and (–)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability.
        Cancer Epidemiol Biomark Prev. 2002; 11: 1025-1032
        • Yang C.S.
        Inhibition of carcinogenesis by tea.
        Nature. 1997; 389: 134-135
        • Yang C.S.
        • Chen L.
        • Lee M.J.
        • Balentine D.
        • Kuo M.C.
        • Schantz S.P.
        Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers.
        Cancer Epidemiol Biomarkers Prev. 1998; 7: 351-354
        • Scalbert A.
        • Williamson G.
        Dietary intake and bioavailability of polyphenols.
        J Nutr. 2000; 130: 2073S-2085S
        • Adhami V.M.
        • Malik A.
        • Zaman N.
        • et al.
        Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo.
        Clin Cancer Res. 2007; 13: 1611-1619
        • Lambert J.D.
        • Lee M.J.
        • Diamond L.
        • et al.
        Dose-dependent levels of epigallocatechin-3-gallate in human colon cancer cells and mouse plasma and tissues.
        Drug Metab Dispos. 2006; 34: 8-11
        • Goodin M.G.
        • Rosenberg R.J.
        Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse.
        Toxicol Sci. 2003; 76: 262-270
        • Chow H.H.
        • Cai Y.
        • Hakim I.A.
        • et al.
        Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.
        Clin Cancer Res. 2003; 9: 3312-3319
        • Ullmann U.
        • Haller J.
        • Decourt J.P.
        • Girault J.
        • Richard-Caudron A.S.
        • Pineau B.
        A single ascending dose study of epigallocatechin gallate in healthy volunteers.
        J Int Med Res. 2003; 31: 88-101