Impaired antioxidant enzyme functions with increased lipid peroxidation in epithelial ovarian cancer

IUBMB Life. 2017 Oct;69(10):802-813. doi: 10.1002/iub.1675. Epub 2017 Sep 8.

Abstract

We aimed to identify the possible role of oxidant-antioxidant status in epithelial ovarian cancer (EOC) by measuring (a) antioxidant enzyme (AOE) activities [total superoxide dismutase (SODtotal ), manganese-SOD (Mn-SOD), copper,zinc-SOD (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx1)], (b) Mn-SOD protein expression, (c) lipid peroxidation markers [malondialdehyde (MDA), 8-epi-prostaglandin-F2α (8-epi-PGF2α)] and by evaluating the possible correlations between tumor biomarkers, reproductive hormone levels and all measured parameters, comprehensively. The data obtained from the patients with EOC (M, n = 26) evaluated according to the histopathological/clinical characteristics of tumors and compared with data of healthy controls [Ctissue (C1) and Cblood/urine (C2), n = 30, respectively). Significantly, low activities of tumor SODtotal (52%), Mn-SOD (42%), Cu,Zn-SOD (55%); high activities of tumor and erythrocyte CAT (66%, 33% respectively) and tumor GPx1 (60%); high levels of tumor Mn-SOD protein expression; tumor MDA (193%) and urinary 8-epi-PGF2α (179%) were observed in serous EOC tumors (M1, n = 18) compared with controls (P < 0.05). However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors. Obtained data indicate the presence of a severe redox imbalance in EOC and draw attention to the criticial role of AOEs in the pathogenesis of the disease. © 2017 IUBMB Life, 69(10):802-813, 2017.

Keywords: catalase; epithelial ovarian cancer; glutathione peroxidase; lipid peroxidation; oxidative stress; superoxide dismutase.

MeSH terms

  • Antioxidants / metabolism
  • Carcinoma, Endometrioid / diagnosis
  • Carcinoma, Endometrioid / enzymology*
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Catalase / genetics
  • Catalase / metabolism*
  • Cystadenocarcinoma, Serous / diagnosis
  • Cystadenocarcinoma, Serous / enzymology*
  • Cystadenocarcinoma, Serous / pathology
  • Dinoprost / analogs & derivatives
  • Dinoprost / urine
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Gene Expression
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism*
  • Glutathione Peroxidase GPX1
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lipid Peroxidation
  • Malondialdehyde / blood
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / diagnosis
  • Neoplasms, Glandular and Epithelial / enzymology*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology
  • Progesterone / blood
  • Prolactin / blood
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism*
  • Testosterone / blood

Substances

  • Antioxidants
  • Isoenzymes
  • SOD1 protein, human
  • 8-epi-prostaglandin F2alpha
  • Testosterone
  • Progesterone
  • Estradiol
  • Malondialdehyde
  • Prolactin
  • Follicle Stimulating Hormone
  • Dinoprost
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase-1
  • Glutathione Peroxidase GPX1
  • GPX1 protein, human