The Interplay between Oxidative Stress and Sphingolipid Metabolism in Endometrial Cancer

Abstract

Endometrial cancer is one of the most common malignancies in women. Sphingolipids, a group of lipids, play a key role in cancer biology. Cancer cells often exhibit abnormal redox homeostasis characterized by elevated levels of reactive oxygen species (ROS). Emerging evidence suggests that ceramides are involved in inhibiting proliferation and inducing apoptosis through ROS production. However, there is no data on the relationship between sphingolipid metabolism and oxidative status in endometrial cancer. The present study aims to assess the content of individual sphingolipids and oxidative status in healthy women and those with endometrial cancer. Sphingolipid analysis was performed using mass spectrometry. Total oxidative status (TOS) and total antioxidant capacity (TAC) were assessed colorimetrically. Our results showed a significant increase in the levels of all measured sphingolipids in cancer tissues compared to healthy endometrium. Additionally, a significant decrease in the S1P/ceramide ratio (sphingolipid rheostat) was observed in cancer patients, particularly for C14:0-Cer, C16:0-Cer, C18:1-Cer, C22:0-Cer, and C24:0-Cer. Furthermore, increased TOS and decreased TAC were found in cancer patients compared to healthy women. Significant correlations were observed between the levels of individual sphingolipids and oxidative status, with the strongest correlation noted between C22:0-Cer and TOS (r = 0.64). We conclude that endometrial cancer is characterized by profound changes in sphingolipid metabolism, contributing to oxidative dysregulation and tumor progression.

Keywords: endometrial cancer; mass spectrometry; oxidative status; sphingolipids.

Figure 1

The overview of sphingolipid metabolism. SPT—serine palmitoyltransferase, ROS—reactive oxygen species.

Figure 2

(A–I) Sphingolipid rheostat—the ratio of S1P concentration (pmol/mg tissue) to ceramide concentration (pmol/mg tissue). Data are presented as medians (interquartile range) and the differences between groups were compared by the Mann–Whitney U test; ** p < 0.01, **** p < 0.0001 indicate significant differences from the controls.

Figure 3

(A) The value of total oxidative status (TOS) (µmol/L), (B) total antioxidant capacity (TAC) (µmol/L), and (C) OSI expressed as [19]: [TOS]/[TAC] × 100%. Data are presented as medians (interquartile range). Analysis was performed with the Mann–Whitney U test; ** p < 0.01, **** p < 0.0001 indicate significant differences from the controls.