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Resveratrol Prevents Hormone-refractory Prostate Cancer Cell Growth via Inhibition of STAT3 Activity

STAT3 활성 억제를 유도하는 resveratrol의 호르몬 불응성 전립선 암 예방 효과

  • Cho, Seok-Cheol (Department of Food Science and Engineering, Seowon University) ;
  • Choi, Bu Young (Department of Pharmaceutical Science and Engineering, Seowon University)
  • 조석철 (서원대학교 바이오융합학부 식품공학과) ;
  • 최부영 (서원대학교 바이오융합학부 제약공학과)
  • Received : 2014.05.29
  • Accepted : 2014.07.07
  • Published : 2014.08.31

Abstract

The mechanisms underlying the refractory effects of flutamide, a first-line oral anti-androgen drug, have not been entirely elucidated. In the present study, we investigated the mechanism of flutamide-induced hormone-refractory prostate cancer cell growth and its modulation by resveratrol, a phytoalexin present in grapes. Resveratrol significantly attenuated interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) transcriptional activity and dihydrotestosterone (DHT) or IL-6-induced prostate-specific antigen (PSA) transcriptional activity. Furthermore, compared to treatment with DHT or IL-6 alone, combination treatment of cells significantly increased PSA transcriptional activity, and resveratrol markedly diminished DHT plus IL-6-induced STAT3 and PSA transcriptional activities. Thus, the inhibitory effects of resveratrol on IL-6-, DHT-, and flutamide-induced hormone-refractory prostate cancer cell growth are partly mediated by the suppression of STAT3 reporter gene activity, suggesting that resveratrol represents a promising therapy for prostate cancer.

전립선암은 발병률이 높은 암종 중에 하나이다. 전립선 치료제인 flutamide는 androgen 수용체의 호르몬 치료제로서 내성효과에 대한 기본 메커니즘은 명확하지 않다. 본 연구에서는 flutamide에 의해 유도되는 호르몬 불응성 전립선 암세포 성장에서 포도 성분인 resveratrol의 억제효과를 조사하였다. 본 연구의 결과를 통해 호르몬 비의존적인 신호전달의 전환으로 유발되는 호르몬 불응성 전립선 암에서 resveratrol은 예방 및 항암효과에 기여할 것이라 판단된다.

Keywords

References

  1. De Wit R. Chemotherapy in hormone-refractory prostate cancer. BJU Int. 101 (Suppl. 2): 11-15 (2008)
  2. Keizman D, Maimon N, Gottfried M. Metastatic hormone refractory prostate cancer: Recent advances in standard treatment paradigm, and future directions. Am. J. Clin. Oncol. 37: 289-296 (2012)
  3. Alexandre I, Rixe O. Hormone-refractory prostate cancer. Ann. Urol. (Paris) 41: 47-55 (2007) https://doi.org/10.1016/j.anuro.2007.02.003
  4. Oudard S, Banu E, Scotte F, Beuzeboc P, Guyader C, Medioni J. New targeted therapies in hormone-refractory prostate cancer. Bull. Cancer 94: F62-68 (2007)
  5. Hadaschik BA, Gleave ME. Therapeutic options for hormonerefractory prostate cancer in 2007. Urol. Oncol. 25: 413-419 (2007) https://doi.org/10.1016/j.urolonc.2007.05.010
  6. Lee SO, Lou W, Johnson CS, Trump DL, Gao AC. Interleukin-6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway. Prostate 60: 178-186 (2004) https://doi.org/10.1002/pros.20045
  7. Bavaresco L. Role of viticultural factors on stilbene concentrations of grapes and wine. Drugs Exp. Clin. Res. 29: 181-187 (2003)
  8. Delmas D, Lancon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: A promising molecule for fighting cancer. Curr. Drug Targets 7: 423-442 (2006) https://doi.org/10.2174/138945006776359331
  9. Quoc Trung L, Espinoza JL, Takami A, Nakao S. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition. PLoS One 8: e55183 (2013) https://doi.org/10.1371/journal.pone.0055183
  10. Shakibaei M, Harikumar KB, Aggarwal BB. Resveratrol addiction: to die or not to die. Mol. Nutr. Food Res. 53: 115-128 (2009) https://doi.org/10.1002/mnfr.200800148
  11. Tsakalozou E, Eckman AM, Bae Y. Combination effects of docetaxel and doxorubicin in hormone-refractory prostate cancer cells. Biochem. Res. Int. 2012: 832059 (2012)
  12. Shinohara N. Bisphosphonate against patients with hormone refractory prostate cancer. Nihon Rinsho Jpn J. Clin. Med. 69 (Suppl. 5): 576-580 (2011)
  13. Crawford ED, Rosenblum M, Ziada AM, Lange PH. Hormone refractory prostate cancer. Urology 54: 1-7 (1999)
  14. Malhotra M, Dhingra R, Sharma T, Deep A, Narasimhan B, Phogat P, Sharma PC. Cabazitaxel: A novel drug for hormone-refractory prostate cancer. Mini Rev. Med. Chem. 13: 915-920 (2013) https://doi.org/10.2174/1389557511313060011
  15. Turitto G, Di Bisceglie M, Moraca L, Sasso N, Sepede C, Suriano A, Romito S. Abiraterone acetate: A novel therapeutic option in hormone-refractory prostate cancer. Recenti Prog. Med. 103: 74-78 (2012)
  16. Pitts WR, Jr. The use of flutamide as a single antiandrogen treatment for hormone-refractory prostate cancer. BJU. Int. 93: 1119-1120 (2004) https://doi.org/10.1111/j.1464-410X.2004.4834j.x
  17. Beitzinger M, Hofmann L, Oswald C, Beinoraviciute-Kellner R, Sauer M, Griesmann H, Bretz AC, Burek C, Rosenwald A, Stiewe T. p73 poses a barrier to malignant transformation by limiting anchorage-independent growth. EMBO J. 27: 792-803 (2008) https://doi.org/10.1038/emboj.2008.13
  18. Sun H, Taneja R. Analysis of transformation and tumorigenicity using mouse embryonic fibroblast cells. Methods Mol Biol. 383: 303-310 (2007)

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