The benzimidazole antihelmintic agent, fenbendazole (FZ), displays anti-neoplastic effects in cancer cell lines. It causes G2/M arrest and apoptosis in 5-FU-sensitive SNU-C5 cells and enhances both p53-dependent and -independent apoptosis in 5-FU resistant SNU-C5/5-FUR CRC cells.
However, its mechanism of action remains unclear. Moreover, we found that fenbendazole induces autophagy via Beclin-1 in both CRC cells.
Background
Fenbendazole is a broad-spectrum benzimidazole anthelmintic drug that is used in many animals. It is a relatively safe drug that can induce multiple intracellular changes, including microtubule depolymerization and inhibition of cell cycle progression. However, its anticancer effects have yet to be fully understood.
In this study, we investigated the anticancer effects of fenbendazole in human colorectal cancer cells. We found that fenbendazole induces apoptosis and G2/M arrest via the p53-p21 pathways in SNU-C5 and SNU-C5/5-FUR CRC cells. The phosphorylation state of p53 and ERK were also increased by fenbendazole. However, the phosphorylation state of MLKL was not affected by fenbendazole treatment.
Recently, false information that an anthelmintic drug used to treat parasites in animals cured a patient’s lung cancer spread online. This event raised awareness that antiparasitic drugs might have potential as cancer treatments. While research into anthelmintics has continued, no peer-reviewed studies have confirmed that they can cure cancer. However, some anthelmintics show promising results and may be candidates for repurposing as cancer treatments.
Methods
The objective of this study is to examine cancer patients’ acquisition pattern and perception of false information about fenbendazole. The study focused on three main questions: (1) the process of acquiring fenbendazole-related information and general cancer information daily, (2) the quality of obtained information, and (3) the perceived value of information.
Interviews with cancer patients were conducted, and a semi-structured questionnaire was used to collect data. The results revealed that the majority of cancer patients obtained fenbendazole information through independent channels, such as YouTube. Furthermore, the study also revealed that cancer patients acquire a great deal of information on alternative medicine through social media and various online channels.
Benzimidazole anti-cancer agents inhibit cell growth by binding to beta-tubulin and disrupting microtubules. This drug also induces apoptosis and cell cycle arrest by triggering p21 expression. To further explore its mechanism of action, the viability and apoptosis of wild type and 5-fluorouracil-resistant SNU-C5 cells were evaluated after fenbendazole treatment.
Results
Benzimidazole anthelmintic agents are relatively non-toxic to normal cells and can be used as cancer therapy due to their low half-maximal inhibitory concentration (IC50) in human tumor cells. Recently, benzimidazole has been repurposed for treatment of resistant cancers by enhancing p53-mediated apoptosis and triggering other cell death pathways including autophagy, ferroptosis and necroptosis.
This study aims to examine how cancer patients acquire information about fenbendazole and general cancer on a daily basis, what kind of information they receive, and how they perceive this information. The results indicate that cancer patients acquire information from different sources in a step-by-step manner and the quality of this information is diverse.
The toxicity of fenbendazole may be related to its ability to induce ferroptosis in colorectal cancer cells. Ferroptosis is a form of programmed cell death that is characterized by lipid peroxidation and requires activation of Glutathione Peroxidase 4 (GPX4). In addition, fenbendazole has been shown to inhibit the growth of human colon cancer organoids in vitro by enhancing apoptosis and inhibiting the proliferation of these cells via p53-dependent and -independent pathways.
Conclusions
Fenbendazole (FZ) is a broad-spectrum benzimidazole anthelmintic drug that has been used in many animal species. It is known to inhibit cell growth by causing apoptosis through its microtubule depolymerizing activity. However, little is known about its anti-cancer effects in human cancers.
To investigate the anti-cancer properties of FZ, we assessed its cytotoxicity in wild-type and 5-fluorouracil (FFU) resistant colorectal cancer cells using flow cytometry and Western blotting. We found that FZ induced cell death in both wild-type and FFU resistant SNU-C5 cells through multiple mechanisms.
We speculate that the FZ-induced cell death is mediated by interfering with the energy metabolism of cancer cells by blocking glucose uptake. It also induces necroptosis by triggering the phosphorylation of MLKL. Based on our findings, we propose that a new strategy to overcome resistance to conventional therapies might involve the combination of FZ and other drugs such as radiotherapy or chemotherapy. Furthermore, our data suggest that experts or health authorities should provide evidence-based information promptly when a celebrity’s article on a treatment method becomes a social issue.fenbendazole stage 4 cancer