The Testing Evidence for Using Mebendazole for Treating Melanoma

Executive Summary

• This article covers the evidence I could find for Fenbendazole as a treatment for Melanoma.

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 Fenbendazole and related drugs versus Melanoma.

Many articles on this website cover the evidence for the benefits of Fenbendazole for cancer. But the question of which specific cancers Fenbendazole 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

Cancer Type #8: Melanoma

The following quote is from the article G2 / M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells.

Fenbendazole (FBZ) is a benzimidazole drug that is used as an anthelmintic to treat various parasitic diseases in animals. It is generally regarded as safe with minimal side effects in dogs compared to the other anthelminthic drugs (Dogra et al., 2018).

In addition, a study in human melanoma cells indicated that FBZ also exhibits anti-cancer effects by modulating several cellular pathways (Dogra et al., 2018).

Different studies have shown various FBZ effective doses in canine cancer cells, including canine glioma and canine osteosarcoma cells (Lai et al., 2017; Schmit, 2013). A study that looked at human non-small cell lung carcinoma (A549 cell) showed strong reduction in cell viability (Dogra et al., 2018).

This study showed FBZ induced G2/M arrest and increased tetraploid cells, along with evidence of apoptosis. When cancer cells are treated with MTAs, they can enter three possible conditions: (i) mitotic cell death, (ii) multi-nucleated tetraploid cells and post-slippage death or (iii) senescence escape (Cheng & Crasta, 2,017).

In addition, the term mitotic catastrophe is also used to describe more complicated cell fates. Although mitotic catastrophe is not fully understood, it is defined as cell death resulting from aberrant mitosis and may represent an oncosuppressive mechanism that is distinctive from apoptosis, necrosis or senescence (Portugal et al., 2009; Vitale et al., 2011). Based on our results, FBZ induced some cells to enter an apoptotic pathway, while other cells escaped senescence and became >4N cells. These results suggest that the cells underwent mitotic slippage and post-slippage cell death, indicative of mitotic catastrophe.

Interestingly, although the five melanoma cell lines were arrested in the G2 / M phase, they exhibited distinct morphological changes at different treatment concentrations. UCDK9M3 cells showed G2 / M arrest at 0.5 μM treatment, but it did not have mitotic slippage. The other four cell lines showed mitotic slippage and multinucleation at 1 μM.

In conclusion, FBZ treatment in canine melanoma cells was effective in inducing G2 / M arrest and mitotic slippage, along with an apoptotic effect leading to mitotic catastrophe. Further in vivo studies are needed to determine potential clinical relevance of these findings.

Mitotic slippage eventually leads to cell death.

The following quote is from the article Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells.

Our findings have several important implications. Benzimidazole derivatives ABZ and FBZ stimulate the activity of p53 in malignant melanoma and breast cancer cells overexpressing MdmX.

Our data provide the first evidence that this enhancement occurs, at least in part, through MdmX and Mdm2 downregulation. This points out the significance of MdmX in p53 regulation in tumors that overexpress this essential negative p53 regulator, such as the majority of malignant melanomas.

p53 activation — is a mechanism of apoptosis promotion.

The following quote is from the article Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells.

Most metastatic melanoma patients fail to respond to available therapy, underscoring the need for novel approaches to identify new effective treatments. In this study, we screened 2,000 compounds from the Spectrum Library at a concentration of 1 μmol / L using two chemoresistant melanoma cell lines (M-14 and SK-Mel-19) and a spontaneously immortalized, nontumorigenic melanocyte cell line (melan-a). We identified 10 compounds that inhibited the growth of the melanoma cells yet were largely nontoxic to melanocytes.

Strikingly, 4 of the 10 compounds (mebendazole, albendazole, fenbendazole, and oxybendazole) are benzimidazoles, a class of structurally related, tubulin-disrupting drugs. Mebendazole was prioritized to further characterize its mechanism of melanoma growth inhibition based on its favorable pharmacokinetic profile.

Our data reveal that mebendazole inhibits melanoma growth with an average IC50 of 0.32 μmol / L and preferentially induces apoptosis in melanoma cells compared with melanocytes.

We have identified mebendazole as a potentially effective agent in the treatment of melanoma. We showed that mebendazole has selective cytotoxicity against a panel of melanoma cell lines, whereas it has a minimal effect on the growth of melanocytes.

Selective toxicity against cancer cells means that the healthy cells are left alone.

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.

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.

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?