Celastrol promotes apoptotic cell death in thyroid cancer cells through a caspases-dependent pathway

Celastrol, a naturally occurring bioactive compound, has demonstrated potential in treating inflammation, obesity, and tumors, particularly in colorectal, gastric, and breast cancers. However, its therapeutic effects on thyroid cancer (TC), which have poor clinical outcomes, remain unclear. This study aimed to investigate Celastrol's potential in treating thyroid cancer using cell lines. The viability and proliferation of thyroid cancer cells treated with or without Celastrol were analyzed by CCK-8 and colony formation assay. The state of thyroid cancer cells treated with or without Celastrol were observed by microscopy. Further evidence from flow cytometry and TUNEL staining demonstrated the induction of apoptotic processes in thyroid cancer cells. The expression of PARP1, Caspase-3, Bax, BCL2 in thyroid cancer cells after indicated treatment was analyzed by Western blot and Caspase-3 expression in thyroid cancer cells after 12 and 24 h of Celastrol treatment was detected by immunofuorescence assay. Anaplastic thyroid cancer growth-limiting of Celastrol was evaluated in nude mice. Celastrol induction promoted apoptotic in TC cells, increased the expression of PARP1, Bax and Caspase-3 and reduces expression of BCL2 by Western Blot. The expression of Caspase-3 was increased by immunofluorescence, which indicating that Celastrol may serve as an adjuvant therapeutic agent for thyroid cancer treatment by inducing apoptosis through the caspase-3 pathway. Celastrol treatment of mice implanted with anaplastic thyroid cancer cells also inhibited tumor growth, associated with reduced Ki-67 and increased Caspase-3. Celastrol promotes apoptotic cell death in thyroid carcinoma cells by the Caspase-3 pathway. • Celastrol has been found to promote apoptotic cell death in thyroid cancer cells, offering potential for the development of new anti-cancer drugs. • The anti-cancer effect of Celastrol is known. The ability of Celastrol to promote apoptosis in thyroid cancer does our manuscript adds. • Utilizing Celastrol as a therapeutic drug for thyroid cancer may provide a new treatment option, particularly for patients who are unresponsive to conventional approaches. This discovery holds promise for improving survival rates and quality of life for thyroid cancer patients.