Fenbendazole (FZ), a broad-spectrum anti-parasitic drug used in veterinary medicine, can effectively kill cancer cells without disturbing normal human cells. According to a recent study published in Scientific Reports, the anti-parasitic compound works by disrupting microtubule dynamics and altering cellular pathways that regulate cell growth and proliferation. The research team led by Dr Nishita Mukhopadhyay of National Centre for Human Genome Studies and Research, Panjab University, found that FZ induced p53 activation by interacting with tubulin and also interfering with glucose uptake by inhibiting expression of GLUT transporters and key glycolytic enzymes. It also blocked the growth of human xenografts in nu/nu mice model when given orally.

The study was performed using human non-small cell lung carcinoma (NSCLC) cells A549 and H460. During the experiment, FZ was encapsulated into a PEG-b-PCL micelle for delivery to target cells. The micelles were characterized by light scattering and transmission electron microscopy. Drug release profiles from the micelles were measured spectrophotometrically by measuring turbidity at 340 nm. The results showed that the micelles exhibited a bimodal distribution of fenbendazole and rapamycin with a higher release from FEN-loaded micelles compared to RAPA-loaded ones.

Benzimidazole carbamates, including fenbendazole, interact with the microtubule network by inhibiting its polymerization. Previous studies have shown that fenbendazole is able to induce mitotic catastrophe in mammalian cells by interfering with the interaction of cyclin B1 with cyclin-dependent kinase 1 (CDK1). To determine whether fenbendazole affects mammalian microtubules, A549 and H460 cells were treated with different concentrations of FZ for 24 h. After the treatment, cells were analyzed for cell cycle progression and mitotic catastrophe. During the analysis, A549 cells were synchronized by serum starvation and then treated with 1 uM FZ. The resulting cells were then processed for immunofluorescence and stained with anti-tubulin antibody with a counter staining of propidium iodide. Results indicated that the FZ treatment partially altered the microtubule cage around the nucleus compared to the control mock treated cells (Fig. 1).

To further confirm the above observations, a clonogenic assay was conducted to evaluate the ability of different formulations of FEN and RAPA to inhibit A549 cancer cell growth. The data showed that the mPEG-b-PCL micelles encapsulating FEN and RAPA had the highest ability to suppress cancer cell growth compared to other formulations. The results from the clonogenic assays showed that mPEG-b-PCL containing FEN and RAPA was able to deliver the drug at the tumor site, resulting in an efficient anti-tumor effect. fenbendazole cancer

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