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Vol. 63 No. 8: Issue 8

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Carnosol inhibits Hedgehog signaling pathway in both LNCaP and DU145 prostate cancer cell lines

https://doi.org/10.14715/cmb/2017.63.8.22
H. Gao
Department of Urology, the Dalian Central Hospital, Dalian, China
Q. Song
Department of Urology, the Affiliated Hospital of Dalian Medical University, Dalian, China
J. Yang
Department of Urology, the Affiliated Hospital of Dalian Medical University, Dalian, China
S. Yu
Department of Urology, the Dalian Central Hospital, Dalian, China
J. Zhao
Department of Urology, the Affiliated Hospital of Dalian Medical University, Dalian, China
G. Yu
Department of Urology, the Dalian Central Hospital, Dalian, China

Corresponding Author(s) : G. Yu

hg2445@163.com

Cellular and Molecular Biology, Vol. 63 No. 8: Issue 8

Abstract

To investigate the effect of carnosol on the Hedgehog (HH) signaling pathway in human hormone-dependent prostate cancer cell line LNCaP and hormone-independent prostate cancer cell line DU145. The expression levels of glioma-associated oncogene homolog 1 (Gli1) and Sonic hedgehog (Shh) in human prostate cancer tissues were detected by immunohistochemistry. After treated with carnosol (0.25-16 μmol/L), the cell survival of LNCaP and DU145 cells were detected by MTT assay. The expression levels of Gli1 and Shh mRNA and protein in the two cells were detected by qRT-PCR and western blot, respectively. The apoptosis was determined by the caspase-3 activity assay. Results showed that Shh and Gli1 were upregulated in cancer tissues. The inhibitory effect of carnosol on cell survival was enhanced with concentration, suggesting both LNCaP and DU145 cells were sensitive to carnosol. The inhibitory effects of carnosol on Gli1 and Shh mRNAs in the hormone-dependent LNCaP prostate cancer cell was stronger than that in the hormone-independent DU145 prostate cancer cells. Carnosol downregulated the expression of Gli1 in nucleus, and Shh in cells. Greater carnosol concentration resulted in lower levels of Gli1 and Shh. Carnosol increased caspase-3 activity in a dose-dependent manner, suggesting that carnosol promotes cell apoptosis. Thus, carnosol can inhibit the proliferation and induce the apoptosis of prostate cancer cells in vitro, and its mechanism might be associated with the inhibiting of HH signaling pathway. Although the inhibitory effect of carnosol on hormone-dependent LNCaP prostate cancer cells is stronger than hormone-independent DU145 prostate cancer cells, carnosol might be a potential drug for hormone-independent prostate cancer.

Keywords

Carnosol Prostate cancer Hedgehog signaling pathway Gli1 "‹"‹Shh.
Gao, H., Song, Q., Yang, J., Yu, S., Zhao, J., & Yu, G. (2017). Carnosol inhibits Hedgehog signaling pathway in both LNCaP and DU145 prostate cancer cell lines. Cellular and Molecular Biology, 63(8), 104–108. https://doi.org/10.14715/cmb/2017.63.8.22
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References
  1. Ita K. Percutaneous penetration of anticancer agents: Past, present and future. Biomed Pharmacother 2016; 84:1428-39.
  2. Adeloye D, David RA, Aderemi AV, Iseolorunkanmi A, Oyedokun A, Iweala EE, Omoregbe N, Ayo CK. An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis. PLoS One 2016; 11:e0153496.
  3. Tawfik A. Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Economic Analysis. Ont Health Technol Assess Ser 2015; 15:1-37.
  4. Poomakkoth N, Issa A, Abdulrahman N, Abdelaziz SG, Mraiche F. p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer. J Transl Med 2016; 14:14.
  5. Evans-Axelsson S, Timmermand OV, Bjartell A, Strand SE, Elgqvist J. Radioimmunotherapy for Prostate Cancer--Current Status and Future Possibilities. Semin Nucl Med 2016; 46:165-79.
  6. Xu YM, Liu HZ. [Related biomarkers in the diagnosis of prostate cancer]. Zhonghua Nan Ke Xue 2015; 21:937-40.
  7. Tonyali S, Yazici S. Does solitary- and organ-confined metastasectomy really improve survival in advanced urologic malignancies? Int Urol Nephrol 2016; 48:671-80.
  8. Weng CJ, Yen GC. Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev 2012; 38:76-87.
  9. Petiwala SM, Johnson JJ. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity. Cancer Lett 2015; 367:93-102.
  10. Ngo SN, Williams DB, Head RJ. Rosemary and cancer prevention: preclinical perspectives. Crit Rev Food Sci Nutr 2011; 51:946-54.
  11. Johnson JJ. Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett 2011; 305:1-7.
  12. Mace K, Offord EA, Harris CC, Pfeifer AM. Development of in vitro models for cellular and molecular studies in toxicology and chemoprevention. Arch Toxicol Suppl 1998; 20:227-36.
  13. Khuda-Bukhsh AR, Das S, Saha SK. Molecular approaches toward targeted cancer prevention with some food plants and their products: inflammatory and other signal pathways. Nutr Cancer 2014; 66:194-205.
  14. Kashyap D, Kumar G, Sharma A, Sak K, Tuli HS, Mukherjee TK. Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends and advancements. Life Sci 2017; 169:27-36.
  15. Gonzalez-Vallinas M, Reglero G, Ramirez de Molina A. Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy. Nutr Cancer 2015; 67:1221-9.
  16. Ferris-Tortajada J, Berbel-Tornero O, Garcia-Castell J, Ortega-Garcia JA, Lopez-Andreu JA. [Dietetic factors associated with prostate cancer: protective effects of Mediterranean diet]. Actas Urol Esp 2012; 36:239-45.
  17. Chun KS, Kundu J, Chae IG, Kundu JK. Carnosol: a phenolic diterpene with cancer chemopreventive potential. J Cancer Prev 2014; 19:103-10.
  18. Akaberi M, Mehri S, Iranshahi M. Multiple pro-apoptotic targets of abietane diterpenoids from Salvia species. Fitoterapia 2015; 100:118-32.
  19. Shigemura K, Fujisawa M. Hedgehog signaling and urological cancers. Curr Drug Targets 2015; 16:258-71.
  20. Lin X, Aslam A, Attar R, Yaylim I, Qureshi MZ, Hasnain S, Qadir MI, Farooqi AA. Signaling lansdscape of prostate cancer. Cell Mol Biol (Noisy-le-grand) 2016; 62:45-50.
  21. Yang Z, Peng YC, Gopalan A, Gao D, Chen Y, Joyner AL. Stromal hedgehog signaling maintains smooth muscle and hampers micro-invasive prostate cancer. Dis Model Mech 2017; 10:39-52.
  22. Peng YC, Joyner AL. Hedgehog signaling in prostate epithelial-mesenchymal growth regulation. Dev Biol 2015; 400:94-104.
  23. !!! INVALID CITATION !!! [23].
  24. Zeng YE, Yao XH, Yan ZP, Liu JX, Liu XH. Potential signaling pathway involved in sphingosine-1-phosphate-induced epithelial-mesenchymal transition in cancer. Oncol Lett 2016; 12:379-82.
  25. Zeng Y, Yao X, Chen L, Yan Z, Liu J, Zhang Y, Feng T, Wu J, Liu X. Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/ syndecan-1/TGF-β autocrine loop. Oncotarget 2016; 7:63324-37.
  26. Wu M, Ingram L, Tolosa EJ, Vera RE, Li Q, Kim S, Ma Y, Spyropoulos DD, Beharry Z, Huang J, et al. Gli Transcription Factors Mediate the Oncogenic Transformation of Prostate Basal Cells Induced by a Kras-Androgen Receptor Axis. J Biol Chem 2016; 291:25749-60.
  27. Mazumdar T, Sandhu R, Qadan M, DeVecchio J, Magloire V, Agyeman A, Li B, Houghton JA. Hedgehog signaling regulates telomerase reverse transcriptase in human cancer cells. PLoS One 2013; 8:e75253.
  28. Lin H, Jackson GA, Lu Y, Drenkhahn SK, Brownstein KJ, Starkey NJ, Lamberson WR, Fritsche KL, Mossine VV, Besch-Williford CL, et al. Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract. Cell Biol Int 2016; 40:131-42.
  29. Li J, Chong T, Wang Z, Chen H, Li H, Cao J, Zhang P, Li H. A novel anticancer effect of resveratrol: reversal of epithelialmesenchymal transition in prostate cancer cells. Mol Med Rep 2014; 10:1717-24.
  30. !!! INVALID CITATION !!! [10, 11].
  31. Uttley L, Whyte S, Gomersall T, Ren S, Wong R, Chambers D, Tappenden P. Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics 2016.
  32. Kruk J, Aboul-Enein H. What Are the Links of Prostate Cancer with Physical Activity and Nutrition? : A Systematic Review Article. Iran J Public Health 2016; 45:1558-67.
  33. Campora S, Campazzi E, Zanardi S, Puntoni M, Piccininno M, Piccardo A, Shoushtari Zadeh Naseri M, Defferrari C, Provinciali N, Petrera M, et al. Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer. Transl Oncol 2016; 9:600-5.
  34. Lu Y, Starkey N, Lei W, Li J, Cheng J, Folk WR, Lubahn DB. Inhibition of Hedgehog-Signaling Driven Genes in Prostate Cancer Cells by Sutherlandia frutescens Extract. PLoS One 2015; 10:e0145507.
  35. Lim A, Shin K, Zhao C, Kawano S, Beachy PA. Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate. Nat Cell Biol 2014; 16:1135-45.
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