Enhancement of Paclitaxel's Anticancer Efficacy in Thyroid Cancer by Isodeoxyelephantopin Through Modulation of Oxidative Stress

This study demonstrates that IDET enhances the efficacy of paclitaxel (taxol) against thyroid cancer by inducing reactive oxygen species (ROS)-mediated apoptosis. IDET synergizes with taxol to inhibit proliferation, migration, and invasion of thyroid cancer cells while sparing normal thyroid cells from cytotoxic effects. Mechanistically, the combination treatment downregulates p62 and upregulates Keap1, leading to suppression of Nrf2 signaling and antioxidant gene expression. This disruption of redox homeostasis leads to elevated ROS levels, which trigger apoptosis. In vivo, IDET significantly enhances the antitumor effects in a thyroid cancer xenograft mouse model, resulting in increased oxidative stress and apoptosis through inhibition of the p62-Keap1-Nrf2 pathway. Importantly, IDET exhibits minimal toxicity to major organs and does not adversely affect hematological parameters, indicating a favorable safety profile. These findings suggest that targeting the p62-Keap1-Nrf2 axis to disrupt redox balance represents an effective strategy to overcome chemoresistance. IDET emerges as a promising chemosensitizer for improving therapeutic outcomes in thyroid cancer treatment.