Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells

Sci Rep. 2020 Jul 27;10(1):12505. doi: 10.1038/s41598-020-68668-x.

Abstract

Inadequate nutrient intake leads to oxidative stress disrupting homeostasis, activating signaling, and altering metabolism. Oxidative stress serves as a hallmark in developing prostate lesions, and an aggressive cancer phenotype activating mechanisms allowing cancer cells to adapt and survive. It is unclear how adaptation and survival are facilitated; however, literature across several organisms demonstrates that a reversible cellular growth arrest and the transcription factor, nuclear factor-kappaB (NF-κB), contribute to cancer cell survival and therapeutic resistance under oxidative stress. We examined adaptability and survival to oxidative stress following nutrient deprivation in three prostate cancer models displaying varying degrees of tumorigenicity. We observed that reducing serum (starved) induced reactive oxygen species which provided an early oxidative stress environment and allowed cells to confer adaptability to increased oxidative stress (H2O2). Measurement of cell viability demonstrated a low death profile in stressed cells (starved + H2O2), while cell proliferation was stagnant. Quantitative measurement of apoptosis showed no significant cell death in stressed cells suggesting an adaptive mechanism to tolerate oxidative stress. Stressed cells also presented a quiescent phenotype, correlating with NF-κB nuclear translocation, suggesting a mechanism of tolerance. Our data suggests that nutrient deprivation primes prostate cancer cells for adaptability to oxidative stress and/or a general survival mechanism to anti-tumorigenic agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological* / drug effects
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Culture Media, Serum-Free
  • Humans
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress* / drug effects
  • Phenotype
  • Prostatic Neoplasms / pathology*
  • Protein Transport / drug effects

Substances

  • Antineoplastic Agents
  • Culture Media, Serum-Free
  • NF-kappa B