• May 30, 2024

Anti-Cancer Effect of Benzimidazole in Stage 4 Colorectal Cancer

Benzimidazole, an antihelmintic drug commonly used for treatment of parasitic diseases, has been recently reported to exhibit anticancer activity in several cancers [1]. Among them, fenbendazole (FZ) exerted anti-tumor effect by inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells. Furthermore, fenbendazole increased apoptosis through caspase-3-poly(ADP-ribose) polymerase (PARP) pathways in HCT116 and SW480 cells. In addition, fenbendazole inhibited tumor initiation and metastasis in ApcMin/+ mice model of familial adenomatous polyposis by decreasing c-Myc expression and increasing apoptosis mediated by activated JNK pathway.

In the present study, we investigated the anti-cancer effect of FZ on colorectal cancer cells by evaluating the effects on cell cycle progression, mitochondrial injury and necroptosis. SNU-C5 and SNU-C5/5-FUR colorectal cancer cells were treated with various concentrations of fenbendazole (0.5 and 5 mM for SNU-C5 and SNU-C5/5-FUR, respectively) for 3 days and then subjected to MTT assay to determine cell viability.

Cells were serum starved for 48 h and then treated with the indicated concentration of fenbendazole for different time intervals. After that, cell lysates were collected and immunoblotted with the specific antibodies. The protein bands were quantified and analyzed using AzureSpot analysis software.

FZ induced G2/M arrest and apoptosis in 5-FU-sensitive SNU-C5 cells and in 5-FU resistant SNU-C5/5-FUR cells through p53-p21 pathways. However, fenbendazole did not induce G2/M arrest and apoptosis through p53-p21 pathways in p53 mutant cells. In addition, fenbendazole reduced glucose uptake and caused mitochondrial injury in cancer cells by inhibiting AMPK activation. Moreover, fenbendazole augmented ferroptosis and autophagy and suppressed necroptosis in 5-FU resistant cells. fenbendazole stage 4 cancer

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