Chrysoeriol Inhibits Viability and Triggers Caspase-dependent Apoptosis in Thyroid Cancer TPC-1 Cells

Thyroid cancer represents the most prevalent endocrine cancer, with papillary thyroid carcinoma responsible for the most cases and presenting a significant clinical challenge due to its variable prognosis. This work aims to examine the effects of chrysoeriol on thyroid cancer TPC-1 cells, by targeting apoptotic mediators caspase-3, caspase-8, and caspase-9 through molecular docking and evaluating their expression in TPC-1 cells treated with chrysoeriol under in vitro conditions. The cytotoxic effects of chrysoeriol on the growth of thyroid cancer TPC-1 cells were assessed using an MTT assay. The extent of apoptosis in both untreated and chrysoeriol-treated TPC-1 cells was examined using a dual staining approach. The activity of caspase enzymes (caspase-3, caspase-8, and caspase-9) in untreated and chrysoeriol-exposed TPC-1 cells was assessed using commercial test kits. In addition, the potential interactions of chrysoeriol and doxorubicin (DOX) with the caspase-3, caspase-8, and caspase-9 were evaluated by implementing molecular docking studies. The treatment of diverse dosages of chrysoeriol effectively inhibited thyroid cancer TPC-1 cells in a dose-dependent manner. Moreover, chrysoeriol treatment markedly increased apoptosis in TPC-1 cells, as demonstrated by the results of the dual staining method. Furthermore, treatment with chrysoeriol also increased the activity of caspase-3, caspase-8, and caspase-9 in thyroid cancer TPC-1 cells. Molecular docking predicted a better interaction of caspase-3 (binding affinity (BA) = −6.7 kcal/mol; RMSD = 1.307Å), caspase-8 (BA = −6.5 kcal/mol; RMSD = 1.709Å), caspase-9 (BA = −6.6 kcal/mol; RMSD = 2.08Å) with the chrysoeriol and caspase-3 (BA = −6.3 kcal/mol; RMSD = 2.757Å), caspase-8 (BA = −6.3 kcal/mol; RMSD = 2.398Å), caspase-9 (BA = −6.7 kcal/mol; RMSD = 2.685Å) with the DOX. These computational results suggest that chrysoeriol may interact well with caspase proteins and contribute to their activation as part of its pro-apoptotic mechanism and caspase activation in thyroid cancer TPC-1 cells. The present study demonstrates that chrysoeriol exhibits anti-cancer properties against thyroid cancer, inhibiting cell growth and inducing apoptosis in TPC-1 cells by upregulating caspase activity. The increased activities of caspase-3, caspase-8, and caspase-9 indicate that chrysoeriol activates both intrinsic and extrinsic apoptotic pathways. Molecular docking and toxicity analysis further support these findings by revealing better binding affinities between chrysoeriol and the caspase proteins than DOX, suggesting that these interactions may facilitate caspase activation. Thus, the current results highlight that chrysoeriol is a hopeful anti-cancer agent for future thyroid cancer treatment.