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.
Highlights
Inadequate nutrient intake leads to oxidative stress disrupting homeostasis, activating signaling, and altering metabolism
To study the role of serum deprivation in adaptive survival during oxidative stress in prostate cancer, we first visualized the phenotype of serum-containing and serum-deprived prostate cancer cell lines, and the phenotype of serum-deprived cell lines stimulated with hydrogen peroxide (H2O2), our model of oxidative stress[34,35,36]
For the PC3 and DU145 cell lines, this data suggests that serum deprivation may induce an adaptation to oxidative stress and promote long-term survival in more aggressive cancer cells
Summary
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; literature across several organisms demonstrates that a reversible cellular growth arrest and the transcription factor, nuclear factorkappaB (NF-κB), contribute to cancer cell survival and therapeutic resistance under oxidative stress. When a tumor’s growth exceeds its vascular supply, tumor cells must adapt to a lower availability of nutrients and oxygen resulting in a reversible cell growth arrest (quiescence)[18] This quiescent phenotype is fundamental to tissue renewal and regeneration, as well as protecting against stress and toxicities, which is essential for long-lived cell types such as tumor and stem cells[19,20]. There is difficulty in isolating these unique cells from patients due to limited understanding of cellular quiescence in cancer and the challenges in research development of therapies to prevent cancer relapse
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