Konstantin V. Golovine

BACKGROUND: Elevated NF‐κB activity has been previously demonstrated in prostate cancer cell lines as hormone‐independent or metastatic characteristics develop. We look at the effects of piperlongumine (PL), a biologically active alkaloid/amide present in piper longum plant, on the NF‐κB pathway in androgen‐independent prostate cancer cells.METHODS: NF‐κB activity was evaluated using Luciferase reporter assays and Western blot analysis of p50 and p65 nuclear translocation. IL‐6, IL‐8, and MMP‐9 levels were assessed using ELISA. Cellular adhesion and invasiveness properties of prostate cancer cells treated with PL were also assessed.RESULTS: NF‐κB DNA‐binding activity was directly down‐regulated with increasing concentrations of PL, along with decreased nuclear translocation of p50 and p65 subunits. Expression of IL‐6, IL‐8, MMP‐9, and ICAM‐1 was attenuated, and a decrease of cell‐to‐matrix adhesion and invasiveness properties of prostate cancer cells were observed.CONCLUSIONS: PL‐mediated inhibition of NF‐κB activity decreases aggressive growth characteristics of prostate cancer cells in vitro. Prostate 74:177–186, 2014.

Background: Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues. Results: In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells. Conclusions: Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.