Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1573 - 1573
Published: Dec. 20, 2024
Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk resistance development. Melanoma, a highly aggressive form skin characterized by limited treatment options due to chemoresistance, poses considerable challenge for effective management. Here, we test the hypothesis that dietary supplements such as thymoquinone (TQ) curcumin (CU) cooperatively modulate cancer-associated cellular mechanisms inhibit melanoma progression. Through series vitro experiments utilizing A375 cell line, including assessments viability, apoptosis, multicellular tumor spheroid models, reactive oxygen species (ROS) quantification, metabolomics analysis, RNA sequencing, established combined application TQ CU exhibited superior anti-tumor effects compared individual use. Our results indicate combination significantly inhibited viability induced apoptosis more effectively than either agent alone, with optimal synergy observed at concentrations 25 µM 10 against cells. Additionally, markedly elevated ROS levels, selectively activating mitochondrial apoptotic pathway via caspase-9. Differential gene expression analysis further revealed unique synergistic effect treatment, enhanced regulation genes related oxidative stress apoptosis. Notably, pathways signaling redox homeostasis were influenced combination, GPX3, CYP4F11, HSPB8 regulated. Overall, findings suggest that, acts synergistically melanoma; however, experimental clinical studies are required confirm its therapeutic potential.
Language: Английский