5-Bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one targets prostate cancer cells by down-regulating inflammation-related genes
Keywords:Cancer cell, Inflammation-related gene, Prostate
The present study was performed to examine the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the rate of cell proliferation and apoptosis induction in the PC3, human prostate carcinoma cell line. The cell viability was assayed by using sulphorhodamine B staining and apoptosis by annexin V and flow cytometry analyses. The results revealed that BHP treatment in PC3 cells caused a significant reduction in the rate of cell proliferation in dose- and time-dependent manner. Compared to the un-treated cells, the formation of HUVEC tubes was markedly inhibited on treatment with BHP at a concentration of 30 µM. Further investigation revealed the expression of HMGB1, IL-6 and IL-8, pro-inflammatory cytokines was also inhibited on treatment with BHP. Therefore, BHP treatment plays an important role in inducing apoptosis in the prostrate cells and can be of therapeutic value for the prostate cancer treatment.
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860-67.
Dickinson JM. Microbial pyran-2-ones and dihydropyran-2-ones. Nat Prod Rep. 1993; 10: 71-98.
Faulkner DJ. Marine natural products. Nat Prod Rep. 2001; 18: 1-49.
Gnanasekar M, Thirugnanam S, Ramaswamy K. Short hairpin RNA (shRNA) constructs targeting high mobility group box-1 (HMGB1) expression leads to inhibition of prostate cancer cell survival and apoptosis. Int J Oncol. 2009; 34: 425-31.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60: 277-300.
Jensen PR, Fenical W. Strategies for the discovery of secondary metabolites from marine bacteria: Ecological perspectives. Annu Rev Microbiol. 1994; 48: 559-84.
Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res. 2006; 4: 221-33.
McGlacken GP, Fairlamb IJ. 2-Pyrone natural products and mimetics: Isolation, characterisation and biological activity. Nat Prod Rep. 2005; 22: 369-85.
Pfitzenmaier J, Vessella R, Higano CS, Noteboom JL, Wallace D Jr, Corey E. Elevation of cytokine levels in cachectic patients with prostate carcinoma. Cancer 2003; 97: 1211-16.
Poppe SM, Slade DE, Chong KT, Hinshaw RR, Pagano PJ, Markowitz M, Ho DD, Mo H, Gorman RR 3rd, Dueweke TJ, et al., Antiviral activity of the dihydropyrone PNU-140690, a new non-peptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother. 1997; 41: 1058-63.
Thaisrivongs S, Romero DL, Tommasi RA, Janakiraman MN, Strohbach JW, Turner SR, Biles C, Morge RR, Johnson PD, Aristoff PA, et al., Structure-based design of HIV protease inhibitors: 5,6-dihydro-4-hydroxy-2-pyrones as effective, non-peptidic inhibitors. J Med Chem. 1996; 39: 4630-42.
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal. 2008; 10: 1343-74.
Turner SR, Strohbach JW, Tommasi RA, Aristoff PA, Johnson PD, Skulnick HI, Dolak LA, Seest EP, Tomich PK, Bohanon MJ, et al., Tipranavir (PNU-140690): A potent, orally bioavailable non-peptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem. 1998; 41: 3467-76.
Uehara H, Troncoso P, Johnston D, et al. Expression of interleukin-8 gene in radical prostatectomy specimens is associated with advanced pathologic stage. Prostate 2005; 64: 40-49.
Veltri RW, Miller MC, Zhao G, et al., Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer. Urology 1999; 53: 139-47.
Wakui S, Furusato M, Itoh T, et al. Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: A morphometric study. J Pathol. 1992; 168: 257-62.
Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 1993; 143: 401-09.
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