DNA Fragmentation, Caspase 3 and Prostate-Specific Antigen Genes Expression Induced by Arsenic, Cadmium, and Chromium on Nontumorigenic Human Prostate Cells

Abstract

Prostate cancer is one of the most common cancers and the second cause of cancer-related deaths among men. Metals are recognized as chemical carcinogens where chronic exposures to such metals are implicated in the development of cancer, including prostate cancer. This in vitro study demonstrates the relative death sensitivity of prostatic (RWPE-1) cells to arsenic (As), cadmium (Cd), and chromium (Cr) as environmental pollutants through its apoptotic effects and the effect of these chemicals on prostate-specific antigen (PSA) gene expression as a marker for their carcinogecity. RWPE-1 cells were divided into three groups that were treated with As, Cd, and Cr in three replicates, at three different concentrations for each metal for 48 h. A control group consisted of untreated RWPE1 cells was used. Apoptosis was assessed using comet assay and caspase 3 gene expression; meanwhile, PSA gene expression was evaluated by semiqualitative real-time PCR (RT-PCR). One of the novel findings of this study is that arsenic and cadmium at low concentrations decreased apoptosis of RWPE-1 cells in a concentration-dependent manner while chromium induced significant concentration-dependent increase in apoptosis. Yet, at the highest concentrations, apoptosis was relatively more induced by all chemicals. Arsenic was the most chemical inhibiting apoptosis in RWPE-1 cells at low concentration. While at the moderate and highest concentrations, cadmium was the most inhibiting chemical of RWPE-1 cells' apoptosis. No distinct differences between treated and untreated cells for PSA gene expression were observed. It can be concluded that As and Cd, at low concentrations, can reduce apoptosis of prostatic cells in a concentration-dependent manner while chromium induced it; however, all metal salts used in this study did not induce PSA gene expression.

Androgen receptor modulation following combination exposure to brominated flame-retardants

“…MSMB is secreted by the epithelial cells of the prostate, is considered a prostate cancer marker 44 , and is up regulated by DHT and down regulated by DPTE in ductal breast cancer T47D cells 18 . The presence of PSA transcript in RWPE1 cells has been previously reported 45 and its induction by DHT observed in this study was comparatively lower than that observed in LNCaP cells 18 . In a previous study on LNCaP cells we have also shown that DPTE inhibits the expression of PSA transcripts 18 .…”

Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study

“…Biologically, it has been suggested that arsenic exposure increases the risk of prostate cancer through epigenetic mechanisms that increase cell growth and cell survival while decreasing apoptosis. In the prostate specifically, studies of human prostate epithelial cells in culture have demonstrated that low level exposure to inorganic arsenic induces malignant transformations that involve increases in matrix metalloproteinase-9 secretion, 26 inhibition of apoptosis, 27 aberrant genomic DNA methylation, 28 and K-ras oncogene activation and overexpression 29, 30 among others. 17 Additionally, inorganic arsenic exposure stimulates androgen independence, which is often associated with advanced stages of prostate cancer and a poor prognosis due to resistance to certain types of treatment.…”

Blood cadmium levels increase prostate specific antigen and insulin-like growth factor-1 among cadmium exposed workers

“…Barriers to apoptosis of cells are characterized by decreased expression of the caspase 3 gene, p53 oncogenes, decreased RAD51 and increased gadd45 oncogenes and the growth factors c-jun and igf1rb. (18,19) Prostate cell proliferation caused by exposure to Cd increases the PSA synthesis in prostate cells. The prostate is the main source of PSA production.…”