Oya Korkmaz
European Journal of Multidisciplinary Health Sciences - 2026;11(1):0-0
Methotrexate (MTX) primarily kills tumor cells through its antifolate activity, but emerging evidence shows that its cytotoxicity also involves disruption of cellular redox homeostasis and activation of apoptosis pathways. The use of antioxidant supplements during chemotherapy remains controversial, as they may modulate reactive oxygen species (ROS) levels and thereby influence treatment-related cellular damage. This study explored the effects of fucoidan on MTX-induced redox imbalance and apoptosis-related gene expression changes in ER-positive Ishikawa endometrial carcinoma cells. Experimental groups received MTX, fucoidan, or co-treatment for 24 and 48 hour incubation periods. The MTX IC?? was determined using the MTT viability assay, and a sub-IC?? concentration was selected for combination experiments. Cellular viability was assessed via MTT, oxidative membrane damage was evaluated by measuring malondialdehyde (MDA) levels, and at 24 hours, mRNA levels of Bax and Bcl-2 was quantified by qRT-PCR to calculate the Bax/Bcl-2 ratio as an indicator of mitochondrial apoptotic balance. MTX treatment significantly lower cell viability at both 24 and 48 hours and markedly elevated MDA concentrations compared to controls (p<0.001). It also strongly upregulated Bax, downregulated Bcl-2, and increased the Bax/Bcl-2 ratio (p<0.001), reflecting a shift toward pro-apoptotic signaling. Fucoidan alone caused no significant changes in viability, lipid peroxidation, or apoptotic gene expression. However, co-administration of fucoidan with MTX significantly reduced the MTX-induced rise in MDA levels and partially attenuated the rise in the Bax/Bcl-2 ratio relative to MTX alone (p < 0.05). These results demonstrate that MTX disrupts redox balance and promotes mitochondrial apoptosis in Ishikawa cells. Fucoidan partially mitigates MTX-triggered oxidative stress and apoptosis-related transcriptional changes without fully abolishing the drug's cytotoxic effects. This suggests that concurrent antioxidant use can modulate chemotherapy-associated cellular stress responses, emphasizing the need for careful evaluation of antioxidant supplementation during anticancer treatment.
