Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia.
Medicina (Kaunas). 2024 Aug 23;60(9):1379. doi: 10.3390/medicina60091379.
: 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, investigating 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 (IC) of IMBZC on HT29 and SW620 cell growth were determined to be 22.13 µM (6.97 μg/mL) and 15.53 µM (4.89 μg/mL), respectively. IMBZC did not alter the cell growth of normal HEK293 cell lines. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyses 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. : This 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.
结直肠癌（CRC）仍然是一个主要的全球健康问题。尽管化疗是一线治疗方法，但由于 CRC 中出现的药物耐药性，其效果有限。为了克服耐药性并改善 CRC 患者的预后，有必要研究新的治疗方法。
使用人结直肠腺癌细胞（HT29）和转移性 CRC（SW620）细胞系，通过 MTT 细胞毒性、细胞迁移和集落形成测定以及通过 Western blot 和逆转录-定量聚合酶链反应技术监测凋亡相关蛋白和基因表达，评估了新合成的化合物 1-（异丁基）-3-（4-甲基苄基）苯并咪唑氯化物（IMBZC）的潜在抗癌特性。在不同浓度下测试，IMBZC 对 HT29 和 SW620 细胞生长的半最大抑制浓度（IC）分别为 22.13 µM（6.97 µg/mL）和 15.53 µM（4.89 µg/mL）。IMBZC 不改变正常 HEK293 细胞系的细胞生长。此外，IMBZC 抑制细胞迁移并显著降低集落形成，表明其在抑制癌症转移方面具有广阔的应用前景。机制分析表明，IMBZC 处理增加了促凋亡蛋白 p53 和 Bax 的表达，同时降低了抗凋亡蛋白 Bcl-2 和 Bcl-xL 的表达，表明 IMBZC 处理后的 CRC 细胞发生了凋亡，与未处理的细胞相比。此外，将 IMBZC 与常规化疗药物（即 5-氟尿嘧啶、伊立替康和奥沙利铂）联合使用，可增加药物的细胞毒性潜力。
这项研究表明，IMBZC 通过诱导细胞凋亡、抑制癌细胞迁移和集落形成以及增强常规化疗药物的细胞毒性作用，对 CRC 细胞具有显著的抗癌作用。这些发现表明，IMBZC 可能成为治疗 CRC 的一种有前途的化疗药物。应使用体内模型进行进一步研究，以确认 IMBZC 对 CRC 的抗活性。
