Deciphering the apoptotic properties of ergolide, a sesquiterpene lactone form Inula oculus-christi, in hepatocellular carcinoma

Hepatocellular carcinoma is the most common and fatal liver cancer. Chronic liver disease, cirrhosis, and even nonalcoholic fatty liver disease can come up to hepatocellular carcinoma. Regarding the recent interests in natural products as sources of drug discovery, and considering the confirmed role of sesquiterpene lactones against several cancer cells, the effects of ergolide, a sesquiterpene lactone from Asteraceae family, was evaluated against HepG2 hepatocellular carcinoma to reveal the capabilities of this natural compound for confronting liver cancer. Ergolide was isolated from the chloroform extract of Inula oculus-christi aerial parts and its structure was confirmed with NMR data analysis. Proliferation of HepG2 cells treated with ergolide was assessed by MTT method and the IC₅₀ was calculated. Real time- PCR was used for evaluating gene transcription of apoptosis markers caspase 3, caspase 8, caspase 9, Bax and Bcl2. The expression of proteins of the above mentioned markers was assessed with Western blotting technique. The IC₅₀ of 48 h exposure of HepG2 cells to ergolide was found to be 7.2 µM. The pro-apoptotic genes and expression of protein markers of caspase 3, caspase 8, caspase 9, Bax were significantly upregulated at this concentration and even its half (IC_50/2) = 3.6). The anti-apoptotic gene and protein Bcl2 were downregulated at both of these concentrations. Ergolide may represent a promising lead compound in further preclinical investigation for liver cancer studies.

The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01069-6.