Lithocholic Acid-Derived Imidazolium Salts Suppress Breast Cancer Growth: In Vitro and In Vivo Evaluation

A series of imidazolium salts (IMS), substituted with lithocholic acid (LA) and alkyl chains of varying lengths (LA-1 to LA-10), were evaluated for their cytotoxic effects against breast cancer (BC).

The cytotoxic potential of the tested salts was assessed in estrogen-dependent (MCF-7) and non-estrogen-dependent (MDA-MB-231) cell lines, as well as in the cardiomyocyte cell line H9C2. The study was also conducted in vivo using a MCF-7 mouse xenograft model.

The cytotoxicity of IMS increased with the length of the aliphatic chain. A significant effect, compared with the reference drug, was observed for LA-7 and LA-8 (IC₅₀ = 13.07-13.19 µg/ml) in MCF-7 cells and for LA-1-LA-8 (IC₅₀ = 77.82-21.06 µg/mL) in MDA-MB-231 line. LA-8 and doxorubicin showed increased toxicity in MCF-7 cells, reducing HMGB1 concentration and DNA synthesis, while increasing apoptosis and the activation caspase 7 and 8. Most of the tested IMS exhibited significantly lower toxicity toward healthy H9C2 cardiomyocytes (IC₅₀ = 52.09-105.40 µg/mL) compared with doxorubicin (IC₅₀ = 51.71 µg/mL). In vivo studies demonstrated that LA-8 treatment significantly inhibited the growth of MCF-7 tumors.

LA-based IMS demonstrate significant potential as chemotherapeutic agents for the treatment of breast cancer.