A Novel N-heterocyclic Carbene Compound Exhibits Anticancer Properties by Inducing Apoptosis, Inhibiting Cell Migration, and Improving Standard Therapeutic Efficacy in Human Colorectal Cancer Cell Lines

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.