Cancer treatment Research in Fenben
Benzimidazole-based antiparasitic drugs have recently been repositioned as potential treatments for cancers that don't respond to traditional therapies. To assess the effectiveness of benzimidazole against such resistant cancers, researchers studied its impact on colorectal cancer cells that are resistant to 5-fluorouracil, a standard chemotherapy drug. The study employed various assays, including cell viability tests and Western blot analysis, as well as flow cytometry for cell death and cell cycle analysis.
Comparing the effects of fenbendazole and albendazole, two types of benzimidazole anthelmintics, it was found that fenbendazole was more effective against 5-fluorouracil-resistant SNU-C5 colorectal cancer cells. Subsequent flow cytometry tests showed that fenbendazole not only triggered apoptosis, but also arrested the cell cycle at the G2/M phase in both resistant and wild-type cells.
Interestingly, the 5-fluorouracil-resistant SNU-C5 cells displayed less autophagy and heightened levels of ferroptosis and apoptosis enhanced by ferroptosis, compared to their wild-type counterparts. Moreover, these resistant cells had lower levels of caspase-8 and p53 activation. This suggests that fenbendazole could serve as an alternative treatment option for 5-fluorouracil-resistant cancers, and its anticancer effects do not appear to rely on p53 activity in these resistant cells.
These products are used solely for research purposes only. Please read our terms and conditions upon checkout.
One area of research involves exploring the potential anticancer properties of fenbendazole. Studies have shown that fenbendazole exhibits antiproliferative effects on various cancer cell lines in vitro. It has been found to induce cell cycle arrest, inhibit tumor cell growth, and promote apoptosis, potentially through its interference with microtubule dynamics. However, further research is needed to better understand its mechanism of action and its potential application in cancer treatment.
Repurposing approved medications offers a promising avenue for identifying new cancer therapies, particularly for drug-resistant strains. Benzimidazole anthelmintics are noted for their relative safety in normal cells, having an IC50 value of 5 µM in less sensitive cancer cell types. Prior research has highlighted the compound's multi-faceted anti-cancer activity, which includes cell cycle arrest, apoptosis induction, autophagy, and cellular viability alteration.
Self-medication with fenbendazole, a type of benzimidazole, has been reported by cancer patients on social media. Despite some preliminary evidence supporting its anti-cancer capabilities in genitourinary tumors, its use remains controversial due to concerns about toxicity and teratogenic effects. However, its higher safety profile in normal cells versus cancer cells warrants further investigation.
Colorectal cancer (CRC) ranks as the third most commonly diagnosed cancer and second leading cause of cancer-related deaths globally. Resistance to 5-fluorouracil (5-FU), the standard chemotherapy drug for CRC, is a major concern, often linked to mutations in p53 or p38α MAPK genes. Strategies involving the activation of various pathways have been proposed to counter this resistance.
Regarding benzimidazole's role in CRC, existing studies have indicated its efficacy in inhibiting proliferation and inducing apoptosis in multiple CRC cell lines. Compounds like albendazole and mebendazole have shown promising results. However, research on benzimidazole's effectiveness against drug-resistant or metastatic forms of CRC is limited.
Thus, our study aims to investigate the anti-cancer potential and mechanisms of fenbendazole in 5-FU resistant SNU-C5 cells, in comparison to their wild-type counterparts. This could pave the way for new therapeutic approaches to overcome 5-FU resistance in CRC treatment.
The Proven RESULTS in research for colorectal Cancer
Fenbendazole and albendazole showed a concentration-dependent reduction in the growth of two types of colorectal cancer cells: SNU-C5 and SNU-C5/5-FUR. Fenbendazole was more effective against SNU-C5/5-FUR cells and demonstrated increased effectiveness over time. These drugs also affected the cancer cell cycles, leading to a delay at the G2/M phase.
After 3 days of treatment, cell survival rates for SNU-C5 were reduced to around 42% with fenbendazole and 38% with albendazole. For SNU-C5/5-FUR cells, the rates dropped to 66% and 68%, respectively, and further decreased at higher drug concentrations.
Fenbendazole triggered apoptosis, a type of cell death, through the activation of caspase-3 and PARP pathways in these colorectal cancer cells. The drug did not seem to activate other cell death mechanisms. Analysis of proteins related to autophagy and ferroptosis indicated that these pathways were not significantly affected.
The study suggests that fenbendazole could be a promising treatment for colorectal cancer due to its anti-proliferative and apoptosis-inducing effects.
MORE RESEARCH STUDY IN CANCER TREATMENT
This study was in part supported by Leukemia Lymphoma Society grant LLS6175-08, NIH grant CA57341, and by Johns Hopkins Research Animal Resources.
Fenbendazole has also been investigated for its immunomodulatory properties. Research suggests that it may modulate immune responses by affecting cytokine production and immune cell functions. In animal studies, fenbendazole has shown potential immunomodulatory effects by influencing immune cell populations and their activity. These findings indicate a potential role for fenbendazole in immunotherapy and immune-related disorders, but more research is required to elucidate its mechanisms and clinical applications.
Emerging evidence suggests that fenbendazole may have metabolic effects beyond its anthelmintic activity. It has been studied for its potential to influence glucose metabolism, lipid metabolism, and mitochondrial function. Animal studies have shown improvements in glucose tolerance, insulin sensitivity, and lipid profiles following fenbendazole treatment. These findings highlight fenbendazole as a potential research tool for investigating metabolic disorders and exploring therapeutic interventions.
Additional Research Areas:
Fenbendazole has been investigated in various other research areas, including neuroprotection, antiviral activity, and anti-inflammatory effects. Preliminary studies have suggested its neuroprotective potential in neurodegenerative disorders and its antiviral activity against certain viruses. Furthermore, fenbendazole has shown anti-inflammatory effects in experimental models, indicating its potential application in inflammatory conditions.