Establishment of In Vitro and In Vivo Anticolorectal Cancer Efficacy of Lithocholic Acid-Based Imidazolium Salts

Diana Sawicka; Agnieszka Hryniewicka; Sylwia Gohal; Anna Sadowska; Anna Pryczynicz; Katarzyna Guzińska-Ustymowicz; Emilia Sokołowska; Jacek W Morzycki; Halina Car

doi:10.3390/ijms23137019

Establishment of In Vitro and In Vivo Anticolorectal Cancer Efficacy of Lithocholic Acid-Based Imidazolium Salts

Int J Mol Sci. 2022 Jun 24;23(13):7019. doi: 10.3390/ijms23137019.

Authors

Diana Sawicka¹, Agnieszka Hryniewicka², Sylwia Gohal¹, Anna Sadowska¹, Anna Pryczynicz³, Katarzyna Guzińska-Ustymowicz³, Emilia Sokołowska¹, Jacek W Morzycki⁴, Halina Car¹

Affiliations

¹ Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland.
² Department of Organic Chemistry, Medical University of Bialystok, Mickiewicza Street 2A, 15-222 Bialystok, Poland.
³ Department of General Pathomorphology, Medical University of Bialystok, Waszyngtona Street 13, 15-269 Bialystok, Poland.
⁴ Department of Natural Product Chemistry, University of Bialystok, Ciołkowskiego Street 1K, 15-245 Bialystok, Poland.

Abstract

Imidazolium salts (IMSs) are the subject of many studies showing their anticancer activities. In this research, a series of novel imidazolium salts substituted with lithocholic acid (LCA) and alkyl chains of various lengths (S1-S10) were evaluated against colon cancer cells. A significant reduction in the viability and metabolic activity was obtained in vitro for DLD-1 and HT-29 cell lines when treated with tested salts. The results showed that the activities of tested agents are directly related to the alkyl chain length, where S6-S8 compounds were the most cytotoxic against the DLD-1 line and S4-S10 against HT-29. The research performed on the xenograft model of mice demonstrated a lower tendency of tumor growth in the group receiving compound S6, compared with the group receiving 5-fluorouracil (5-FU). Obtained results indicate the activity of S6 in the induction of apoptosis and necrosis in induced colorectal cancer. LCA-based imidazolium salts may be candidates for chemotherapeutic agents against colorectal cancer.

Keywords: colorectal cancer; imidazolium salts; lithocholic acid.

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Apoptosis
Cell Line, Tumor
Colorectal Neoplasms* / drug therapy
Fluorouracil / pharmacology
Fluorouracil / therapeutic use
Humans
Lithocholic Acid / pharmacology
Mice
Salts / pharmacology

Substances

Antineoplastic Agents
Salts
Lithocholic Acid
Fluorouracil

Grants and funding

The authors acknowledge the “Innovation Incubator 2.0” program announced by the Minister of Science and Higher Education, co-financed by the European Union from the European Regional Development Fund. This work was supported by the Medical University of Bialystok, Poland (SUB/3/DN/20/001/3327/2020, SUB/3/DN/22/001/3327).