Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Maria V Fedorova1, Vladimir I Voznesensky2, Elena A Sosnova3

  • 1Central Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 111123 Moscow, Russia.

Biomedicines
|May 25, 2024
PubMed

Insights

Reactive oxygen species (ROS) are implicated in cancer. This study found increased activity of NADH- and NADPH-dependent oxidoreductases (CYB5R and CYPOR) in advanced ovarian cancers, correlating with peritoneal fluid

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Reactive oxygen species (ROS) have a complex role in cancer development.
  • Microsomal NADH- and NADPH-dependent oxidoreductases are key intracellular ROS producers, but their specific involvement in ovarian cancer's oxidative balance remains unclear.

Purpose of the Study:

  • To investigate the activity of cytochrome b5 reductase (CYB5R) and cytochrome P450 reductase (CYPOR) in ovarian cancer tissues and peritoneal fluid.
  • To assess the antioxidant capacity of peritoneal fluid in relation to ovarian cancer progression and differentiation.
  • To explore the correlation between oxidoreductase activity, peritoneal fluid antioxidant capacity, and chemotherapy resistance.

Main Methods:

  • Developed a novel chemiluminescence assay to measure CYB5R and CYPOR activity using NADH and NADPH stimulation.
  • Analyzed ovarian cancer tissues and cells isolated from peritoneal fluid.
  • Quantified the antioxidant capacity of peritoneal fluid.

Main Results:

  • CYB5R and CYPOR activity were significantly elevated in moderately and poorly differentiated ovarian adenocarcinomas compared to well-differentiated types and cystadenomas.
  • Chemotherapy-resistant tumors exhibited lower CYB5R and CYPOR activity than non-resistant tumors.
  • Peritoneal fluid antioxidant capacity increased with tumor severity (benign < well-differentiated < moderately/poorly differentiated), indicating antioxidant excess in advanced cancers.

Conclusions:

  • NAD(P)H oxidoreductases and peritoneal fluid's antioxidant potential play significant roles in ovarian cancer biochemistry.
  • Elevated CYB5R and CYPOR activity correlates with advanced tumor differentiation and peritoneal fluid antioxidant capacity.
  • The studied parameters show promise for ovarian cancer diagnostics and prognostics, with the developed assay applicable to other tissues.

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