Casticin Impacts Key Signaling Pathways in Colorectal Cancer Cells Leading to Cell Death with Therapeutic Implications

Colorectal cancer is the third most frequently encountered cancer worldwide. While current chemotherapeutics help to manage the disease to some extent, they have eluded achieving complete remission and are limited by their severe side effects. This warrants exploration of novel agents that are efficacious with anticipation of minimal adverse effects. In the current study, casticin, a tetramethoxyflavone, was tested for its ability to inhibit the viability of three human colorectal cancer cells: adenocarcinoma (DLD-1, Caco-2 cell lines) and human colorectal carcinoma cells (HCT116 cell line). Casticin showed potent inhibition of viability of DLD-1 and HCT116 cells. Clonogenic assay performed in DLD-1 cells revealed that casticin impeded the colony-forming efficiency of the cells, suggesting its impact on the proliferation of these cells. Further, a sustained effect of the inhibitory action upon withdrawal of the treatment was observed. Elucidation of the mechanism of action revealed that casticin impacted the extrinsic programmed cell death pathway, leading to an increase in apoptotic cells. Further, Bcl-2, the key moiety of cell survival, was affected. Notably, a significant number of cells were arrested in the G2/M phase of the cell cycle in DLD-1 cells. Due to the multifaceted action of casticin, we envision that treatment with casticin could provide an efficacious treatment option for colorectal adenocarcinomas with minimal side effects.