Pathology & Oncology Research

, Volume 25, Issue 1, pp 263–268 | Cite as

A Potential Role for Green Tea as a Radiation Sensitizer for Prostate Cancer

  • Andrew C. Schroeder
  • Huaping Xiao
  • Ziwen Zhu
  • Qing Li
  • Qian Bai
  • Mark R. Wakefield
  • Jeffrey D. Mann
  • Yujiang FangEmail author
Original Article


Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RT-PCR/IHC were used to investigate the mechanisms. We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the anti-proliferative effect of RT/GT correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.


Green tea Prostate cancer Radiation therapy 



This study was supported by grants from Des Moines University for Yujiang Fang, MD. PhD. (IOER 05-14-01 and IOER 112-3749). Andrew C. Schroeder, B. S. was supported by Mentored Research Program from Des Moines University (IOER 112-3113).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30. CrossRefGoogle Scholar
  2. 2.
    Bernard W, Christopher P (2014) World cancer report 2014. International Agency for Research on Cancer. World Health Organization, Lyon, FranceGoogle Scholar
  3. 3.
    Zhang S, Shan L, Li Q, Wang X, Li S, Zhang Y, Fu J, Liu X, Li H, Zhang W (2014) Systematic analysis of the multiple bioactivities of green tea through a network pharmacology approach. Evid Based Complement Alternat Med 2014:512081.
  4. 4.
    Fang Y, DeMarco VG, Nicholl MB (2012) Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell proliferation and promoting cell senescence and apoptosis. Cancer Sci 103(6):1090–1098CrossRefGoogle Scholar
  5. 5.
    Davalli P, Rizzi F, Caporali A, Pellacani D, Davoli S, Bettuzzi S, Brausi M, D’Arca D (2012) Anticancer activity of green tea polyphenols in prostate gland. Oxidative Med Cell Longev 2012:984219.
  6. 6.
    Liang X, Gao J, Sun X, Zhu L, Jia Y, Gu Y, Han C, Zhang X, Hou S (2013) [Tea polyphenols inhibits the proliferation of prostate cancer DU145 cells]. Zhonghua nan ke xue=. Natl J Androl 19(6):495–500Google Scholar
  7. 7.
    Kwak TW, Park SB, Kim H-J, Jeong Y-I, Kang DH (2017) Anticancer activities of epigallocatechin-3-gallate against cholangiocarcinoma cells. OncoTargets Ther 10:137CrossRefGoogle Scholar
  8. 8.
    Naponelli V, Ramazzina I, Lenzi C, Bettuzzi S, Rizzi F (2017) Green tea Catechins for prostate cancer prevention: present achievements and future challenges. Antioxidants 6(2):26CrossRefGoogle Scholar
  9. 9.
    Oya Y, Mondal A, Rawangkan A, Umsumarng S, Iida K, Watanabe T, Kanno M, Suzuki K, Li Z, Kagechika H, Shudo K, Fujiki H, Suganuma M (2017) Down-regulation of histone deacetylase 4, −5 and −6 as a mechanism of synergistic enhancement of apoptosis in human lung cancer cells treated with the combination of a synthetic retinoid, Am80 and green tea catechin. J Nutr Biochem 42:7–16. CrossRefGoogle Scholar
  10. 10.
    Tsai Y-J, Chen B-H (2016) Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3. Int J Nanomedicine 11:1907CrossRefGoogle Scholar
  11. 11.
    Henning SM, Aronson W, Niu Y, Conde F, Lee NH, Seeram NP, Lee R-P, Lu J, Harris DM, Moro A (2006) Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. J Nutr 136(7):1839–1843CrossRefGoogle Scholar
  12. 12.
    Fang Y, Bradley MJ, Cook KM, Herrick EJ, Nicholl MB (2013) A potential role for resveratrol as a radiation sensitizer for melanoma treatment. J Surg Res 183(2):645–653CrossRefGoogle Scholar
  13. 13.
    Fang Y, Braley-Mullen H (2008) Cultured murine thyroid epithelial cells expressing transgenic Fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein are protected from Fas-mediated apoptosis. Endocrinology 149(7):3321–3329CrossRefGoogle Scholar
  14. 14.
    Fang Y, Sharp GC, Braley-Mullen H (2008) Interleukin-10 promotes resolution of granulomatous experimental autoimmune thyroiditis. Am J Pathol 172(6):1591–1602CrossRefGoogle Scholar
  15. 15.
    Fang Y, Wei Y, DeMarco V, Chen K, Sharp GC, Braley-Mullen H (2007) Murine FLIP transgene expressed on thyroid epithelial cells promotes resolution of granulomatous experimental autoimmune thyroiditis in DBA/1 mice. Am J Pathol 170(3):875–887CrossRefGoogle Scholar
  16. 16.
    Fang Y, Moore BJ, Bai Q, Cook KM, Herrick EJ, Nicholl MB (2013) Hydrogen peroxide enhances radiation-induced apoptosis and inhibition of melanoma cell proliferation. Anticancer Res 33(5):1799–1807Google Scholar
  17. 17.
    Fang Y, Herrick EJ, Nicholl MB (2012) A possible role for perforin and Granzyme B in resveratrol-enhanced Radiosensitivity of prostate cancer. J Androl 33(4):752–760CrossRefGoogle Scholar
  18. 18.
    Fang Y, Sharp GC, Yagita H, Braley-Mullen H (2008) A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis. J Pathol 216(4):505–513CrossRefGoogle Scholar
  19. 19.
    Dulaney CR, Osula DO, Yang ES, Rais-Bahrami S (2016) Prostate radiotherapy in the era of advanced imaging and precision medicine. Prostate. Cancer 2016:4897515.
  20. 20.
    Johnson D, Walker C (1999) Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol 39(1):295–312CrossRefGoogle Scholar
  21. 21.
    Nobori T (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Trends Genet 10(7):228CrossRefGoogle Scholar
  22. 22.
    Helgadottir H, Höiom V, Jönsson G, Tuominen R, Ingvar C, Borg Å, Olsson H, Hansson J (2014) High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families. J Med Genet 51(8):545–552CrossRefGoogle Scholar
  23. 23.
    Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE (1994) Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 8(1):27–32CrossRefGoogle Scholar
  24. 24.
    Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA (1995) Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270(5239):1189–1192CrossRefGoogle Scholar
  25. 25.
    Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267(5203):1456CrossRefGoogle Scholar
  26. 26.
    Zhu Z, Zhang D, Lee H, Menon AA, Wu J, Hu K, Jin Y (2017) Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222. J Leukoc Biol 101(6):1349–1359.
  27. 27.
    Zhang H, Xu Q, Krajewski S, Krajewska M, Xie Z, Fuess S, Kitada S, Pawłowski K, Godzik A, Reed JC (2000) BAR: an apoptosis regulator at the intersection of caspases and Bcl-2 family proteins. Proc Natl Acad Sci 97(6):2597–2602CrossRefGoogle Scholar
  28. 28.
    Yip K, Reed J (2008) Bcl-2 family proteins and cancer. Oncogene 27(50):6398–6406CrossRefGoogle Scholar
  29. 29.
    Khanna K, Wie T, Song Q, Burrows S, Moss D, Krajewski S, Reed J, Lavin M (1996) Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in Burkitt's lymphoma cells. Cell Death Differ 3(3):315–322Google Scholar
  30. 30.
    Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S, Reed JC (1996) Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol 148(5):1567Google Scholar
  31. 31.
    Tron V, Krajewski S, Klein-Parker H, Li G, Ho V, Reed J (1995) Immunohistochemical analysis of Bcl-2 protein regulation in cutaneous melanoma. Am J Pathol 146(3):643Google Scholar
  32. 32.
    Tsujimoto Y, Cossman J, Jaffe E, Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228(4706):1440–1443CrossRefGoogle Scholar
  33. 33.
    Yip KW, Shi W, Pintilie M, Martin JD, Mocanu JD, Wong D, MacMillan C, Gullane P, O'Sullivan B, Bastianutto C (2006) Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer. Clin Cancer Res 12(19):5726–5732CrossRefGoogle Scholar
  34. 34.
    Zhu Z, Davidson KT, Brittingham A, Wakefield MR, Bai Q, Xiao H, Fang Y (2016) Trichomonas vaginalis: a possible foe to prostate cancer. Med Oncol 33(10):115CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Andrew C. Schroeder
    • 1
  • Huaping Xiao
    • 1
    • 2
  • Ziwen Zhu
    • 3
  • Qing Li
    • 2
  • Qian Bai
    • 3
  • Mark R. Wakefield
    • 3
  • Jeffrey D. Mann
    • 1
  • Yujiang Fang
    • 1
    • 3
    Email author
  1. 1.Department of Microbiology, Immunology & PathologyDes Moines University College of Osteopathic MedicineDes MoinesUSA
  2. 2.The Affiliated Hospital of Xiangnan UniversityChenzhouChina
  3. 3.Department of SurgeryUniversity of Missouri School of MedicineColumbiaUSA

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