Objective: To investigate the anticancer effects of a novel benzofuran-isatin conjugate N’-(5-methoxy-2-oxoindolin-3-ylidene)-3-methylbenzofuran-2-carbohydrazide (conjugate 5d) against human colorectal adenocarcinoma (CRC) HT29 and metastatic SW620 colorectal cancer cells. Methods: The cytotoxic properties of conjugate 5d were evaluated using the MTT assay. Its anti-oncogenic effects were assessed by real-time monitoring of cell proliferation, migration, and invasion, and by performing a clonogenic assay. Flow cytometry was also used to assess the apoptotic status and cell cycle. Apoptosis, cell cycle, and epithelial-mesenchymal transition-related protein and gene expression levels were also measured. Results: Conjugate 5d exhibited cytotoxic effects on both CRC cells and enhanced the cytotoxic efficacy of 5-fluorouracil, irinotecan, and oxaliplatin. Conjugate 5d also induced apoptosis by modulation of anti-apoptotic ( i.e. , Bcl-xl) and pro-apoptotic ( i.e. , Bax, p53, cytochrome c) proteins, and MMP loss. Docking studies predicted molecular interactions of conjugate 5d with anti-apoptotic Bcl-2, revealing conjugate 5d as a potential Bcl-2 inhibitor. Regarding the oncogenic process, conjugate 5d inhibited CRC cell proliferation, migration, invasion, and colony formation, upregulated E-cadherin expression, and downregulated N-cadherin expression. Conclusions: Conjugate 5d shows significant anticancer effects against HT29 and SW620 cells by exerting pro-apoptotic and antimetastatic activities. It also enhances the cytotoxic efficacy of conventional chemotherapeutic drugs in CRC cell lines. However, in vivo studies should be conducted to further confirm its efficacy.
Abdulla et al. (Fri,) studied this question.