Hindawi Publishing Corporation ISRN Oncology Volume 2013, Article ID 918207, 8 pages http://dx.doi.org/10.1155/2013/918207 Research Article Beyond the Limits of Oxygen: Effects of Hypoxia in a Hormone-Independent Prostate Cancer Cell Line A. C. Mamede, 1,2,3 A. M. Abrantes, 1,3 L. Pedrosa, 1,4 J. E. Casalta-Lopes, 1 A. S. Pires, 1,4 R. J. Teixo, 1,4 A. C. Gonçalves, 3,5 A. B. Sarmento-Ribeiro, 3,5 C. J. Maia, 2 and M. F. Botelho 1,3 1 Biophysics Unit, Institute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal 2 CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilh˜ a, Portugal 3 Centre of Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal 4 Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal 5 Applied Molecular Biology and Hematology Group, Faculty of Medicine, University of Coimbra, Coimbra, Portugal Correspondence should be addressed to A. C. Mamede; ana mamede@hotmail.com Received 24 June 2013; Accepted 13 August 2013 Academic Editors: Y. Akiyama, W. Kildal, and L. Mutti Copyright © 2013 A. C. Mamede et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Prostate cancer (PCa) has a high incidence worldwide. One of the major causes of PCa resistance is intratumoral hypoxia. In solid tumors, hypoxia is strongly associated with malignant progression and resistance to therapy, which is an indicator of poor prognosis. Te antiproliferative efect and induced death caused by doxorubicin, epirubicin, cisplatin, and futamide in a hormone- independent PCa cell line will be evaluated. Te hypoxia efect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All drugs induced an antiproliferative efect and also cell death in the cell line under study. Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia decreases cellular proliferation and migration. Hypoxia can infuence cellular resistance, proliferation, and migration. Tis study shows that hypoxia may be a key factor in the regulation of PCa. 1. Introduction Prostate cancer (PCa) is one of the most common diseases in the world, being the sixth leading cause of cancer death worldwide [1]. Te incidence of PCa varies according to three major risk factors: age, ethnicity, and familial predisposition [2–6]. Hypoxia can be defned as a reduction in oxygen partial pressure (pO 2 ). Tis characteristic constitutes a condition of various pathophysiological states such as ischemic vascular disease, myocardial infarction, stroke, respiratory insuf- ciency, and cancer [7]. Clinically relevant levels of hypoxia are detected in 50% to 60% of solid tumors [8]. Hypoxia results from an imbalance between rate of consumption and supply of oxygen to cancer cells, thus compromising several cellular functions. Cancer cells have the capacity to adapt to hypoxic environments due to various genetic and epigenetic mechanisms and alterations at cellular level that contribute to adaptive changes which lead to a clinically aggressive pheno- type, having hypoxic tumors a poor prognosis. Tese tumors are more difcult to treat, being highly resistant, presenting an increased risk of recurrence and progression [9, 10]. Regarding PCa, intratumoral oxygen levels were evalu- ated through a polarographic electrode with the form of a needle, and it was found that pO 2 in PCa was signifcantly lower (pO 2 = 2.4 mmHg) than in normal tissues (muscle, pO 2 = 30 mmHg) [11]. In fact, increase of hypoxia may be critical in PCa progression and resistance [12]. In this work, we aim at studying the antiproliferative efect and cell death induced by various agents of chemotherapy and hormonal therapy in a human hormone-independent PCa cell line. Response to these treatment agents will be evaluated in normoxia and hypoxia conditions. Chemotherapy is a treatment used in PCa when it stops responding to hormone