In Vitro Investigation of the Relationship between Schistosomiasis and Prostate Cancer

Abstract

Schistosomiasis is a neglected tropical disease that affects 200 million people and accounts for 100, 000 deaths annually. In endemic geographical areas, schistosomiasis has been implicated as an etiological agent in the pathogenesis of bladder, colorectal and renal carcinoma largely due to chronic infection of tissues with Schistosoma eggs. Several studies have also reported cases of association between Schistosoma infection and prostate cancer, one of the most common cancers in men. The possible causal association is however poorly understood. This study therefore aimed at experimentally investigating this association and elucidating the underlying mechanism. Urine samples from individuals living in Galilea, a Schistosomiasis endemic community in the Ga South District of Ghana were collected and screened for Schistosoma infection via microscopy and multiplex PCR. Soluble antigens (SEA) were prepared from Schistosoma-egg positive urine samples and assessed for the ability to induce cancer-like phenotypes including excessive proliferation, oxidative stress (GSH depletion) and diminished apoptosis in cultured human prostate (PNT2) cells. Cell proliferative effect of SEA was evaluated by the tetrazolium-based MTS assay. Oxidative stress-inducing effect of SEA was also determined using the fluorescent probe, O-phthalaldehyde. Apoptosis-diminishing effect of SEA was evaluated via fluorescence (Hoechst) staining and flow cytometry. 14.4% (30/209) schistosomiasis prevalence was recorded. Out of 30 schistosoma-infected persons, 73% (22 persons) recorded light infections whereas 27% (8 persons) were heavily infected. Microscopic and molecular analysis revealed infecting-schistosome species to be S. haematobium and S. mansoni. 63% (19 persons) were infected with S. haematobium only whereas 37% (11 persons) were co-infected. Prostate cell proliferation was significantly induced by 12.5μg/ml SEA (P=0.029). Also, SEA dose-dependently depleted cellular reduced glutathione (GSH). Flow cytometric analysis and fluorescence staining revealed that SEA dose-dependently and significantly diminished apoptosis in prostate cells. Schistosomiasis still remains a major health challenge. Findings of this study suggest that schistosoma-infection may play a role in the pathogenesis of prostate cancer. In vivo studies are however needed to confirm this association.