Nitric Oxide Exposure Induces Prostate Cancer Carcinogenesis and Pro-Tumor Phenotype

By Robert Dillard - Last Updated: August 24, 2022

Prostate cancer is a leading cause of cancer death in men. Inflammation and overexpression of inducible nitric oxide synthase (NOS2) have been implicated in prostate carcinogenesis. A study explored the idea the hypothesis that nitric oxide NO exerts pro-tumorigenic effects on prostate cells at physiologically levels, and a pro-tumor secretory phenotype. The results were published in the journal Nitric Oxide.

In this study, the researchers analyzed the impact of acute exposure of normal prostate cells (RWPE-1) to NO, on prostate cancer cell proliferation and activation of DNA damage repair pathways. The investigators also assessed the long-term impact of chronic NO exposure on RWPE-1 cell migration.

According to the results, NO causes DNA damage through γH2AX foci and p53 activation. This process leads G1/S phase block and activation of 53BP1 DNA damage repair protein, the researchers noted.

“Long term adaption to NO results in increased migration and invasion potential, acquisition of anchorage independent growth and increased resistance to chemotherapy. This was recapitulated in PC3 and DU145 prostate cancer cells, which upon chronic exposure to NO displayed increased cell migration, colony formation and increased resistance to chemotherapeutics. These findings indicate that NO may play a key role in the development of prostate cancer and the acquisition of an aggressive metastatic phenotype,” the researchers concluded.