Prostate cancer is the most common form of cancer affecting men in the Western world. Risk factors include ageing, genetics, recurrent inflammation, life and diet intake, related to an increase of oxidative stress. Prostate cancer risk is also associated with exposure to carcinogen such as polycyclic aromatic hydrocarbons (PAHs), originated from the incomplete combustion of carbon-containing fuels like tobacco, wood, diesel, or charbroiled meat. Although numerous studies have associated the effect of PAHs to tumour development, few investigations have associated its effects to cancer progression. Considering that prostate cancer patients don’t die from localized prostate cancer but from advanced disease, we are interested in investigating whether PAHs may potentially influence prostate cancer progression and how this could be related to an increase in oxidative stress. Likewise we evaluated the effect of PAHs (pyrene, benzo(a)pyrene, chrysene and benzo(k)fluoranthene) on cell growth and in the expression of molecules involved in cancer metastization such as the vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) using prostatederived cell lines from localized adenocarcinoma (HPV10), bone metastasis (PC3) and in non-neoplastic prostate epithelium cells. Moreover, we evaluated oxidative stress parameters, assessing reactive oxygen species (ROS) production and reduced glutathione content. Our data clearly demonstrates that PAHs can stimulate cell growth, particularly in localized cancer cells and induce an increase of VEGF and HIF expression. These results are concomitant with an increase of ROS production, suggesting that PAHs exposure may participate in prostate cancer progression, in part, due to an increase of ROS. Therefore this study suggests that PAHs exposure should be avoided to prevent prostate cancer progression.
Cite this paper
M. Freitas, V. Alves, A. Sarmento-Ribeiro and A. Mota-Pinto, "Polycyclic Aromatic Hydrocarbons May Contribute for Prostate Cancer Progression," Journal of Cancer Therapy, Vol. 4 No. 4, 2013, pp. 37-46. doi: 10.4236/jct.2013.44A005.
 R. Siegel, D. Naishadham and A. Jemal, “Cancer Statistics, 2012,” CA: A Cancer Journal for Clinicians, Vol. 62, No. 1, 2012, pp. 10-29. doi:10.3322/caac.20138
 W. G. Nelson, T. L. DeWeese and A. M. DeMarzo, “The Diet Inflammation, and the Development of Prostate Cancer,” Cancer and Metastasis Reviews, Vol. 21, No. 1, 2002, pp. 3-16. doi:10.1023/A:1020110718701
 A. M. De Marzo, E. A. Platz, S. Sutcliffe, J. Xu, H. Gr?nberg, C. G. Drake, Y. Nakai, W. B. Isaacs and W. G Nelson, “Inflammation in Prostate Carcinogenesis,” Nature Reviews Cancer, Vol. 7, No. 4, 2007, pp. 256-269.
 A. Minelli, I. Bellezza, C. Conte and Z. Culig, “Oxidative Stress-Related Aging: A Role for Prostate Cancer?” Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, Vol. 1795, No. 2, 2009, pp. 83-91.
 O. Yossepowitch, I. Pinchuk, U. Gur, A. Neumann, D. Lichtenberg and J. Baniel, “Advanced But Not Localized Prostate Cancer Is Associated with Increased Oxidative Stress,” Journal of Urology, Vol. 178, No. 4, 2007, pp. 1238-1244. doi:10.1016/j.juro.2007.05.145
 H.-W. Lim, S. Hong, W. Jin, S. Lim, S.-J. Kim, H.-J. Kang, E.-H. Park, K. Ahn and C.-J. Lim, “Up Regulated of Defense Enzymes Is Responsible for Low Reactive Species in Malignant Prostate Cancer Cells,” Experimental and Molecular Medicine, Vol. 37, No. 5, 2005, pp. 497-506. doi:10.1038/emm.2005.62
 M. Freitas, I. Baldeiras, T. Proen?a, V. Alves, A. MotaPinto and A. Sarmento-Ribeiro, “Oxidative Stress Adaptation in Aggressive Prostate Cancer May Be Counteracted by the Reduction of Glutathione Reductase,” FEBS Open Bio, Vol. 2, 2012, pp. 119-128.
 IARC, “Polynuclear Aromatic Compounds, Part 1. Chemical, Environmental and Experimental Data,” IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Vol. 32, International Agency for Research on Cancer, Lyon, 1983.
 IARC, “Some Non-Heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, Vol. 92,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC, WHO, Lyon, 2010.
 H. Enokida, H. Shiina, S. Urakami, M. Terashima, T. Ogishima, L. C. Li, M. Kawahara, M. Nakagawa, C. J. Kane, P. R. Carroll , M. Igawa and R. Dahiya, “Smoking Influences Aberrant CpG Hypermetilation of Multiple Genes in Human Prostate Carcinoma,” American Cancer Society, Vol. 106, No. 1, 2005, pp. 79-86.
 A. Chaudhary, T. Pechan and K. L. Willett, “Differential Protein Expression of Peroxidation I and II by Benzo (a)Pyrene and Quercetin Treatment in 22Rv1 and PrEC Prostate Cell Lines,” Toxicology and Applied Pharmacology, Vol. 220, No. 2, 2006, pp. 197-210.
 R. Singh , R. J. Sramb, B. Binkova, I. Kalina, T. A. Popov, T. Georgieva, S. Garte, E. Taioli and P. B. Farmer, “The Relationship between Biomarkers of Oxidative DNA Damage, Polycyclic Aromatic Hydrocarbon DNA Adducts, Antioxidant Status and Genetic Susceptibility Following Exposure to Environmental Air Pollution in Humans,” Mutation Research, Vol. 620, No. 1-2, 2007, pp. 83-92. doi:10.1016/j.mrfmmm.2007.02.025
 H. Pelicano, D. Carney and P. Huang, “ROS Stress in Cancer and Therapeutic Implications,” Drug Resistance Updates, Vol. 7, No. 2, 2004, pp. 97-110.
 J. S. Clerkin, R. Naughton, C. Quiney and T. G. Cotter, “Mechanisms of ROS Modulated Cell Survival during Carcinogenesis,” Cancer Letters, Vol. 226, No. 1, 2008, pp. 30-36. doi:10.1016/j.can let.2008.02.029
 X. Lin, M. Tascilar, W. H. Lee, W. J. Vles, B. H. Lee, R. Veeraswamy, K. Asgari, D. Freije, B. van Rees and W. R. Gage, “GSTP1 CpG Island Hypermethylation Is Responsible for the Absence of GSTP1 Expression in Human Prostate Cancer Cells,” American Journal of Pathology, Vol. 159, No. 5, 2001, pp. 1815-1826.
 O. Hankinson, “The Aryl Hydrocarbon Receptor Complex,” Annual Review of Pharmacology and Toxicology, Vol. 35, 1995, pp. 307-340.
 M. Haque, J. Francis and I. Sehgal, “Aryl Hydrocarbon Exposure Induces Expression of MMP-9 in Human Prostate Cancer Cell Lines,” Cancer Letters, Vol. 225, No. 1, 2005, pp. 159-166. doi:10.1016/j.canlet.2004.11.043
 O. Alqawi, M. Moghaddas and G. Singh, “Effects of Geldanamycin on HIF-1α Mediated Angiogenesis and Invasion in Prostate Cancer Cells,” Prostate Cancer and Prostatic Diseases, Vol. 9, No. 2, 2006, pp. 126-135.
 M. Kilic, H. Kasperczyk, S. Fulda and K.-M. Debatin, “Role of Hypoxia Inducible Factor-1 Alfa in Modulation of Apoptosis Resistance,” Oncogene, Vol. 26, No. 14, 2007, pp. 2027-2038. doi:10.1038/sj.onc.1210008
 B. Nicholson, G. Schaefer and D. Theodorescu, “Angiogenesis in Prostate Cancer: Biology and Therapeutic Opportunities,” Cancer and Metastasis Reviews, Vol. 20, No. 3-4, 2002, pp. 297-319. doi:10.1023/A:1015543713485
 S. Fulda, “HIF-1-Regulated Glucose Metabolism in the Control of Apoptosis Signalling,” Expert Review of Endocrinology & Metabolism, Vol. 3, No. 3, 2008, pp. 303-308. doi:10.1586/174466188.8.131.523
 A. Lekas, A. C. Lazaris, C. Deliveliotis, M. Chrisofos, C. Zoubouli, D. Lapas, T. Papathomas, I. Fokitis and L. Nakopoulou, “The Expression of Hypoxia-Inducible Factor-1alpha (HIF-1Alpha) and Angiogenesis Markers in Hyperplastic and Malignant Prostate Tissue,” Anticancer Research, Vol. 26 No. 4B, 2006, pp. 2989-2993.
 P. C. Weijerman, J. J. Konig, S. T. Wong, H. G. Niesters and D. M. Peehl, “Lipofection-Mediated Immortalization of Human Prostatic Epithelial Cells of Normal and Malignant Origin Using Human Papillomavirus Type 18 DNA,” Cancer Research, Vol. 54, No. 21, 1994, pp. 5579-5583.
 M. E. Kaighn, K. S. Narayan, Y. Ohnuki, J. F. Lechner and L. W. Jones, “Establishment and Characterization of a Human Prostatic Carcinoma Cell Line (PC3),” Investigative Urology, Vol. 17, No. 1, 1979, pp. 16-23.
 D. Bello, M. M. Webber, H. K. Kleinman, D. D. Wartinger and J. S. Rhim, “Androgen Responsive Adult Human Prostatic Epithelial Cell Lines Immortalized by Human Papillomavirus 18,” Carcinogenesis, Vol. 18, No. 6, 1997, pp. 1215-1223. doi:10.1093/carcin/18.6.1215
 M. Freitas, V. Alves, A. B. Sarmento-Ribeiro and A. Mota-Pinto, “Combined Effect of Sodium Selenite and Docetaxel on PC3 Metastatic Prostate Cancer Cell Line,” Biochemical and Biophysical Research Communications, Vol. 408, No. 4, 2011, pp. 713-719.
 G. Rothe and G. Valet, “Flow Cytometric Analysis of Respiratory Burst Activity in Phagocytes with Hydroethidine and 2,7 Dichlorofluorescein,” Journal of Leuko cyte Biology, Vol. 47, No. 5, 1990, pp. 440-448.
 M. Lodovici, V. Akpan, C. Evangelisti and P. Dolara, “Sidestream Tobacco Smoke as the Main Predictor of Exposure to Polycyclic Aromatic Hydrocarbons,” Journal of Applied Toxicology, Vol. 24, No. 4, 2004, pp. 277-228.
 W. Qi, H. Liu, J. Qu, C. Hu, H. Lan, M. Berg, H. Ren and W. Xu, “Polycyclic Aromatic Hydrocarbons in Effluents from Wastewater Treatment Plants and Receiving Streams in Tianjin, China,” Environmental Monitoring and Assessment, Vol. 177, No. 1-4, 2011, pp. 467-480.
 M. Oliva, M. L. G. deCanales, C. Gravato, L. Guilhermino and J. A. Perales, “Biochemical Effects and Polycyclic Aromatic Hydrocarbons (PAHs) in Senegal Sole (Soleasenegalensis) from a Huelva Estuary (SWSpain),” Ecotoxicology and Environmental Safety, Vol. 73, No. 8, 2010, pp. 1842-1851. doi:10.1016/j.ecoenv.2010.08.035
 M. Plísková, J. Vondrácek, B. Vojtesek, A. Kozubík and M. Machala, “Deregulation of Cell Proliferation by Polycyclic Aromatic Hydrocarbons in Human Breast Carcinoma MCF-7 Cells Reflects Both Genotoxic and Nongenotoxic Events,” Toxicological Sciences, Vol. 83, No. 2, 2005, pp. 246-256. doi:10.1093/toxsci/kfi040
 K. M. Lau, M. La Spina, J. Long and S. M. Ho, “Expression of Estrogen Receptor-Alpha and Estrogen Receptor-Beta in Normal and Malignant Prostatic Epithelial Cells: Regulation by Methylation and Involvement in Growth Regulation,” Cancer Research, Vol. 60, No. 12, 2000, pp. 3175-3182.
 J. Bouchal, F. R. Santer, P. P. S. Hoschele, E. Tomastikova, H. Neuwirt and Z. Culig, “Transcriptional Coactivators p300 and CBP Stimulate Estrogen Receptor-Beta Signaling and Regulate Cellular Events in Prostate Cancer,” Prostate, Vol. 71, No. 4, 2011, pp. 431-437.
 A. M. Vingaard, C. Hnida and J. C. Larsen, “Environmental Polycyclic Hydrocarbons affect Androgen Receptor Activation in Vitro,” Toxicology, Vol. 145, No. 2-3, 2000, pp. 173-183. doi:10.1016/S0300-483X(00)00143-8
 F. Mehraein-Ghomi, E. Lee, D. R. Church, T. A. Thompson, H. S. Basu and G. Wilding, “JunD Mediates Androgen-Induced Oxidative Stress in Androgen Dependent LNCaP Human Prostate Cancer Cells,” Prostate, Vol. 68, No. 9, 2008, pp. 924-934. doi:10.1002/pros.20737
 S. Koochekpour, “Androgen Receptor Signaling and Mutations in Prostate Cancer,” Asian Journal of Andrology, Vol. 12, No. 5, 2010, pp. 639-657.
 R. B. Marques, N. F. Dit, S. Erkens-Schulze, W. M. van Weerden and G. Jenster, “Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models,” PLoS One, Vol. 19, No. 5, Article ID: e135002010. doi:10.1371/journal.pone.0013500
 B. Kumar, S. Koul, L. Khandrinka, R. B. Meacham and H. K. Koul, “Oxidative Stress Is Inherent in Prostate Cancer Cells and Is Required for Aggressive Phenotype,” Cancer Research, Vol. 68, No. 6, 2008, pp. 1777-1785.
 M. Sundaresan, Z. X. Yu, V. J. Ferrans, K. Irani and T. Finkel, “Requirement for Generation of H2O2 for Platelet-Derived Growth Factor Signal Transduction,” Science, Vol. 270, No. 5234, 1995, pp. 296-299.
 G. A. Murrell, M. J. Francis and L. Bromley, “Modulation of Fibroblast Proliferation by Oxygen Free Radicals,” Biochemical Journal, Vol. 265, No. 3, 1990, pp. 659-665.
 N. S. Chandel, E. Maltepe, E. Goldwasser, C. E. Mathieu, M. C. Simon and P. T. Schumacker, “Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription,” Proceedings of the National Academy of Sciences of the United States, Vol. 95, No. 20, 1998, pp. 11715-11720. doi:10.1073/pnas.95.20.11715
 S. L. Kabler, A. Seidel, J. Jacob, J. Doehmer, C. S. Morrow and A. J. Townsend, “Differential Protection by Human Glutathione S-Transferase P1 against Cytotoxicity of Benzo[a]Pyrene, Dibenzo[A,L]Pyrene, or Their Dihydrodiol Metabolites, in Bi-Transgenic Cell Lines That Coexpress Rat versus Human Cytochrome P4501A1” Chemico-Biological Interactions, Vol. 15, No. 179, 2009, pp. 240-246.