Abstract 890: Nuclear factor kappa B (NF-κB) promotes oxidative stress adaptation and survivorship

Abstract

Abstract Cellular oxidative stress is one of the several hallmarks of the aggressive phenotypes observed in prostate cancer. As levels of reactive oxygen species (ROS) increase, oxidative stressors activate mechanisms allowing cancer cells to adapt and survive. It is unclear how cancer cells adapt and survive oxidative stress; however, literature demonstrates that the transcription factor, nuclear factor-kappa B (NF-κB) contributes to survival during oxidative stress. In cancer, several factors resulting in oxidative stress, including chemotherapy, correlate with NF-κB expression and transcriptional activity, enhancing tumor survivorship and resistance to therapies. We examined adaptability and survivorship to oxidative stress in two common prostate cancer models, DU145 and PC3, which display varying degrees of tumorigenicity, respectively. We observed that serum-starvation induced ROS, stimulating an early oxidative stress environment, and cells further conferred adaptability with the addition of hydrogen peroxide (H202). Measurement of cell viability demonstrated a low death profile in stressed cells, while cell proliferation was stagnant. Quantitative measurement of apoptosis showed no significant cell death in stressed cells suggesting an adaptive mechanism to oxidative stress survival. Consistent with stress adaptation, we observed NF-κB in nuclear fractionations of cell lines which were consistent with nuclear localization observed in other diseases in literature that adapt to oxidative stress. Adaptability to oxidative stress may be a precursor to the inflammatory response in prostate tumor tissues, and/or a general survival mechanism to anti-tumorigenic agents. Acknowledgements: These studies were supported by the NIH/NIGMS/RISE #5R25GM060414-15 and NIH/NIHMD/RCMI #5G12MD007590. Citation Format: Elshaddai White, Jada R. Carter, Cimona V. Hinton. Nuclear factor kappa B (NF-κB) promotes oxidative stress adaptation and survivorship [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 890.