Background: DUSP6 phosphatase serves as a negative regulator of MAPK kinases involved in numerous cellular processes. BCI has been identified as a potential allosteric inhibitor with anticancer activity. Our study was designed to test the anticancer properties of BCI in colon cancer cells, to characterize the effect of this compound on chemotherapeutics such as irinotecan and oxaliplatin activity, and to identify potential molecular targets for this inhibitor. Methods: BCI cytotoxicity, proapoptotic activity, and cell cycle distribution were investigated in vitro on three colon cancer cell lines (DLD1, HT-29, and Caco-2). In silico investigation was prepared to assess BCI drug-likeness and identify potential molecular targets. Results: The exposure of colorectal cancer cells with BCI resulted in antitumor effects associated with cell cycle arrest and induction of apoptosis. BCI exhibited strong cytotoxicity on DLD1, HT-29, and Caco-2 cells. BCI showed no significant interaction with irinotecan, but strongly attenuated the anticancer activity of oxaliplatin when administered together. Analysis of synergy potential further confirmed the antagonistic interaction between these two compounds. In silico investigation indicated CDK5 as a potential new target of BCI. Conclusions: Our studies point to the anticancer potential of BCI but note the need for a precise mechanism of action.
背景：DUSP6磷酸酶作为MAPK激酶的负调控因子，参与多种细胞过程。BCI已被鉴定为一种具有抗癌活性的潜在变构抑制剂。本研究旨在测试BCI在结肠癌细胞中的抗癌特性，分析该化合物对伊立替康和奥沙利铂等化疗药物活性的影响，并确定该抑制剂的潜在分子靶点。方法：在三种结肠癌细胞系（DLD1、HT-29和Caco-2）上体外研究BCI的细胞毒性、促凋亡活性及细胞周期分布。通过计算机模拟分析评估BCI的类药性并识别潜在分子靶点。结果：结直肠癌细胞经BCI处理后产生抗肿瘤效应，表现为细胞周期阻滞和凋亡诱导。BCI对DLD1、HT-29和Caco-2细胞均显示出强烈细胞毒性。BCI与伊立替康联用未产生显著相互作用，但与奥沙利铂联合给药时显著减弱后者的抗癌活性。协同效应分析进一步证实了这两种化合物间的拮抗作用。计算机模拟研究提示CDK5可能成为BCI的新作用靶点。结论：本研究揭示了BCI的抗癌潜力，同时指出需进一步阐明其精确作用机制。
肿瘤(癌症)患者之家