Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation

TL;DR

This study explores how oxidative stress and antioxidant defenses contribute to endometriosis and its progression to cancer.

Contribution

It identifies how redox balance shifts from promoting cell death in benign endometriosis to supporting cancer in its malignant form.

Findings

Oxidative stress from hemoglobin and iron derivatives causes DNA damage in benign endometriosis.

Enhanced antioxidant defenses may promote malignant transformation in endometriosis-associated ovarian cancer.

Redox balance acts as a double-edged sword, influencing both cell death and carcinogenesis.

Abstract

The aim of this study was to investigate the role of redox status in endometriosis and its malignant transformation. A search was conducted between 1990 and 2014 through the English language literature (online MEDLINE PubMed database) using the keywords endometriosis combined with malignant transformation, oxidative stress, and antioxidant defense. In benign endometriosis, autoxidation and Fenton reaction of hemoglobin from the ferrous Fe2+ (oxyhemoglobin) state to the ferric Fe3+ (methemoglobin) state lead to production of excess reactive oxygen species (ROS) such as
O2
− and ∙OH. Hemoglobin, heme, and iron derivatives in endometriotic cysts cause distortion in the homeostatic redox balance. Excess oxidative stress could trigger DNA damage and cell death. In contrast, endometriosis-associated ovarian cancer (EAOC) might be associated with an effective antioxidant defense, including heme oxygenases, cytochrome P450 family, and glutathione transferase family. The pattern of redox balance supports that enhanced antioxidants may be involved in the pathogenesis of malignant transformation. In conclusion, oxidant/antioxidant balance function is a double-edged sword, promoting cell death or carcinogenesis. Upregulation of antioxidant functions in endometriotic cyst may result in restoration of cell survival and subsequent malignant transformation.

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