Nickel chloride has been shown to be a hazardous as category 1 carcinogenic substances, and enhances the lung cancer invasion via E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis, and elevates ANGPTL4/HIF-1α for poor prognosis of lung adenocarcinoma. However, some studies showed that nickel chloride can prevent oral squamous cell carcinoma, and induce hepatocellular carcinoma apoptosis by cleaved Caspase-3. Here we aim to investigate the effect and signaling of the nickel chloride in prostate cancer cells.

Immunofluorescence staining with antibodies and confocal microscopy analysis was performed to study the changes in protein expression or cellular translocation in prostate cancer cell line MyC-CaP-CRL-3255 (ATCC). For cell death and cell cycle analysis, a flow cytometer was used to analyze the PI-Hoechst staining and DNA content.

Nickel chloride at 200 or 600 µM showed the significant induction of cell death in prostate cancer MyC-CaP cells and cell cycle arrest at G1 phase. The cell death induced by nickel chloride was not disrupted or enhanced by ferroptosis inhibitor Fer-1. For cell signaling analysis, we found levels of nuclear localized androgen receptor (AR), and nuclear localized Pim-1 were elevated by treatment of nickel chloride. However, nuclear localized p53, p21, and PARP were decreased upon the treatment.

Nickel chloride at 200 or 600 µM showed the significant induction of cell death in prostate cancer MyC-CaP cells and cell cycle arrest at G1 phase. This type of cell death is not related to ferroptosis but likely related to PARP. The cell cycle arrest is not associated with p53, p21 but through Pim-1 signaling as nuclear Pim-1 regulates cell cycle. Thus, our data suggest that nickel chloride induces cell death in prostate cancer thereby potentiating the application in prostate cancer treatment in clinical treatment.