A new study explored the anticancer effects of Celastrol, a bioactive compound from traditional Chinese medicine, against Adrenocortical Carcinoma using the H295R cancer cell line. Researchers found that Celastrol strongly reduced the survival of cancer cells in a dose-dependent manner, with an IC50 of about 1.63 µM. The compound mainly caused apoptosis, a form of programmed cell death, rather than damaging cells through necrosis or stopping the cell cycle.
The study also showed that Celastrol works in more complex tumor models. It prevented the formation of three-dimensional tumor spheroids and was able to break apart spheroids that had already formed, suggesting potential activity against established tumors. When combined with common ACC treatments such as Mitotane and Etoposide, Celastrol produced additive anticancer effects. However, it showed mild antagonism when used with Cisplatin.
Researchers found that Celastrol works mainly by triggering stress in the cell’s endoplasmic reticulum and activating the integrated stress response. The drug increased levels of stress-related proteins and raised oxidative stress inside cancer cells by greatly reducing the GSH/GSSG balance, leading to a buildup of reactive oxygen species. This stress ultimately pushes the cancer cells toward apoptosis.