The Testing Evidence for Using Mebendazole for Treating Ovarian Cancer

ByShaun Snapp

Executive Summary

  • This article covers the evidence I could find for Mebendazole as a treatment for Ovarian Cancer.

Article Summary

Studies demonstrate that Mebendazole is effective against cancer, we then cover how Mebendazole works against cancer by explaining the mechanisms of action, and then the impacts of Mebendazole on cancer.

Introduction

This article provides an overview covering the evidence for Mebendazole and related drugs versus Ovarian Cancer.

Many articles on this website cover the evidence for the benefits of Mebendazole for cancer. But the question of which specific cancers Mebendazole has been proven effective is a constant source of questions.

The most common Benzimidazoles are Fenbendazole, Mebendazole and Albendazole. In our analysis, we include research for all three drugs together in articles as they are very similar to one another and it improves the ability to tie together different studies. You may see the following terms/acronyms used.

  • FZ or FBZ means Fenbendazole
  • MBZ means Mebendazole
  • AZ means Albendazole

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Cancer Type #6: Ovarian Cancer

The following quote is from the article Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer.

Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models.

Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC.

Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well.

Conclusion: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

The following quote is from the article Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)− b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer.

revious reports in ovarian cancer animal models demonstrated the anti-tumor effect of the IP administration of albendazole, but the drug dose was very high, ranging from 150 mg/kg to 450 mg/kg [111,213], whereas the acceptable dose for the human use of albendazole is up to 400 mg per day [10]. Due to its low water solubility and bioavailability, it must have been used at such a high dose to exhibit a cytotoxic effect. However, the dose was so high that it could be expected to be highly toxic when clinically applied. Therefore, various methods for increasing the solubility of benzimidazole anthelmintics have been proposed. Pourgholami et al. [30] and Pillai et al. [31] suggested attaching cyclodextrin, a cyclic oligosaccharide, to improve the poor aqueous solubility of albendazole. The next concept for improving water solubility was nanoparticle drug delivery systems.

In conclusion, we demonstrated the anti-cancer effects of FZ in various drug delivery modes in EOC models. The natural form of FZ was effective in EOC cells in vitro, but neither oral nor IP administration in vivo had any effect due to the water insolubility of the drug. We combined FZ with PLGA-NPs for the first time. The anti-cancer effects of the water-soluble form of FZ-PLGA-NPs in EOC cells were identified both in vitro and in vivo including in PDX models. Further experiments and clinical trials should be considered in the future for the clinical use of FZ in ovarian cancer treatment.

The following quote is from the article The Effect of Menbendazol on Ovarian Cancer.

Mebendazole inhibited growth of ovarian cancer cell cultures at nanomolar concentrations and PDXs at doses up to 50 mg/kg, and reduced orthotopic tumor establishment at 50 mg/kg. The mechanism of mebendazole was associated with p53-independent induction of p21 and tubule depolymerization. PRIMA-1MET also inhibited tumor establishment and worked synergistically with mebendazole in cell culture to inhibit growth and induce intrinsic apoptosis through a p53- and tubule destabilization-independent mechanism.

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Adding up the Studies of Mebendazole Versus Cancer

There are many studies of Fenbendazole, Mebendazole, Albendazole, and other Benzimidazole derivatives versus cancer.

Due to the success of these studies and the information published in the study publications, the specific mechanisms by which these Benzimidazole-based Anthelmintics work against cancer are at this point well understood. There has not been a study published for every cancer type using one of the Benzimidazole derivatives. There are a very large number of different cancer types and limited funding for this type of research.

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How Many Major Cancer Types Are There Studies For?

When I completed my analysis, I found 18 different types of cancer types which demonstrated effectiveness versus cancer. In many cases, these different cancer types had multiple cancer studies testing the different Benzimidazole derivatives.

Cancer centers do not apply the large body of published studies on the effectiveness of Benzimidazole derivatives to include as part of their treatment offerings. This is true even though Fenbendazole has been demonstrated to improve chemotherapy outcomes.

To understand the mechanisms by which Benzimidazole derivatives work against cancer, see the following few examples. To see all of the known mechanisms that I have compiled from all of the studies see the article on the mechanisms listed below.

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The Multiple Mechanisms by Which Mebendazole Works Against Cancer

There are many ways in which Mebendazole works against cancer including.

  • Reducing metastasis
  • Increase autophagy
  • Increase cancer cell death or apoptosis
  • and much more

This topic is covered in the article By How Many Different Mechanisms Does Menbendazole Fight Cancer?