Zinc Supplementation and Prostate Cancer

Abstract

Prostate cancer continues to be one of the most common fatal cancers in men (Jemal et al., 2010). The comprehensive understanding of the etiology of this disease is however, far from complete because of multitude of genetics and environmental factors involved in the development of this disease (Deutsch et al., 2004; Giovannucci, 2001). One characteristic feature of the prostate gland is its unique ability to accumulate high concentrations of zinc, which may otherwise be toxic to other tissues (Costello & Franklin, 1998). For reasons primarily still unknown, cancerous prostate cells somehow lose its ability to accumulate intracellular zinc concentrations. This is based on consistent observations of low zinc concentrations in malignant prostate tissues as compared to normal prostate and benign prostatic hyperplasia tissues (Feustel & Wennrich, 1984; Ho, 2004; Vartsky et al., 2003; Zaichick et al., 1997). These findings thereby, imply a potential importance of zinc in the pathogenesis of prostate cancer. It is suggested that dietary zinc supplementation protects against oxidative damage, reduces cancer risk (Ho, 2004) and has therapeutic potentials against prostate cancer (Franklin & Costello, 2007). Epidemiologic studies, however, provided contradictory findings on the effectiveness of zinc in prevention against prostate cancer. While there are studies that showed zinc reduces the risk of developing prostate cancer (Key et al., 1997; Kristal et al., 1999), others showed that advanced prostate cancer is associated with high intake of zinc and potentiate the development of benign prostate hyperplasia (BPH) and progression towards cancer (Gallus et al., 2007; Lagiou et al., 1999; Lawson et al., 2007; Leitzmann et al., 2003; Moyad, 2004). Various mechanisms have been proposed to explain how high zinc regulates prostate health and indirectly, how its absence or low concentration could have contributed to the occurrence of prostate cancer. Restoration of high zinc to cancerous prostate tissues has been shown to inhibit prostate cancer cells proliferation (Feng et al., 2002; Feng et al., 2000; Iguchi et al., 1998; Liang et al., 1999) and invasion (Ishii et al., 2004; Ishii et al., 2001a; Ishii et al., 2001b; Uzzo et al., 2006). In contrast, there are studies which showed that zinc under nonphysiological conditions could promote cancer cell growth and invasion (Boissier et al., 2000; Nemoto et al., 2000; Wong & Abubakar, 2008a; Wong & Abubakar, 2010). Because of the diverse roles of zinc in cell signaling, the exact pathways and genes affected by the absence or presence of high zinc concentrations in prostate cancer cells remain unraveled. In an attempt to further understand the complexicity of the role of zinc in prostate cancer, this