Citrinin and Cisplatin Synergistically Induce Apoptosis in Skov3 Ovarian Cancer Cells Via Redox Imbalance and Mitochondrial Dysfunction Publisher



Motafeghi F ; Ghassemi Barghi E ; Gholami Gharab J ; Ghassemibarghi N ; Ramezani Tehrani F
Source: Toxicology Research Published:2025

Abstract

Cisplatin (Cis), a common drug for ovarian cancer therapy, faces limited effectiveness due to drug resistance. Citrinin (CTN), a mycotoxin known to induce oxidative stress, has been proposed as a potential sensitizing agent to enhance cisplatin’s efficacy. This study investigates the effects of CTN on cisplatin-induced cytotoxicity in SKOV3 ovarian cancer cells, examining its mechanisms through redox imbalance, mitochondrial dysfunction, and cytokine-mediated apoptosis. SKOV3 cells were treated with CTN, cisplatin, and their combination. Various parameters were evaluated, including cell viability, DNA damage, oxidative stress (by measuring ROS, MDA, and antioxidant enzymes like SOD, GSH, and CAT), mitochondrial function (via MMP analysis), and levels of inflammatory cytokines (TNF-α, IL-1β, and NF-κB). Apoptosis was also confirmed with the TUNEL assay. The results showed that the combination of CTN and cisplatin significantly increased cytotoxicity and led to a marked reduction in cell viability. This synergistic effect was confirmed by a significant increase in DNA damage and apoptosis. Mechanistically, the combined treatment led to severe redox imbalance, mitochondrial dysfunction, and increased levels of pro-inflammatory cytokines, all of which contributed to the induction of apoptosis. In conclusion, citrinin enhances cisplatin-induced apoptosis in SKOV3 cancer cells by targeting key pathways, including oxidative stress, mitochondrial dysfunction, and the activation of inflammatory responses. These findings suggest that citrinin. © 2025 Elsevier B.V., All rights reserved.