Repurposing Mebendozole As An Anti-cancer Agent And Anti-diabetes Drug

[methylenewhite]

I used mebendozole to reload my metabolism a couple of times. I found it's ability to reverse insulin resistance accidentally, I use it occasionally as antihelmitic drug as I live in third world with low hygienic standarts. First time I used it reversed my blood sugar issues completely in a matter of 2 days. Quick search "mebendozole insulin resistance" gives a proof.

Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies
https://link.springer.com/content/pdf/10.1007/BF00253502.pdf

Fasting plasma glucose concentrations in Type 1 diabetic patients were significantly reduced by I month of mebendazole therapy (12.83 +1.11 versus 6.56_+ 0.56 mmol/l; p< 0.05). These changes occurred despite reduced insulin doses in five out of six Type 1 diabetic patients (83_+ 32 versus 34_+ 8 units/day; NS). In the Type2 diabetic patients, similar decreases in fasting plasma glucose concentrations were observed (10.22_+ 0.56 versus 7.56 + 0.67 mmol/1; p < 0.05). Insulin doses were also reduced in four out of four Type 2 diabetic patients (69 + 23 versus 45 + 12 units/day; NS). Further, chlorpropamide was stopped in one and reduced in two Type 2 diabetic patients. Improvements in fasting plasma glucose concentrations cannot be attributed to weight reduction since four out of six Type 1 diabetic patients gained weight (78 + 12 versus 82 + 13 kg; NS) and two out of six Type 2 diabetic patients gained weight (107 _+ 9 versus 108 ___ 9 kg; NS).

In one presumed Type 1 diabetic patient, the fasting plasma glucose concentration approached normality, and his insulin doses were gradually and persistently decreased throughout a 5-month period after discontinuation of mebendazole. At that time insulin therapy was withdrawn and chlorpropamide therapy was started.


There are some other studies about hypoglycemic effects of mebendazole.

https://www.researchgate.net/public...nd_insulin_secretion_from_isolated_rat_islets
https://www.researchgate.net/public...ycemic_Potential_of_Benzimidazole_Derivatives

Mebendozole causes microtubules degeneration. And this is a way it works in glucose regulation disturbances.

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. - PubMed - NCBI

And microtubules act as a "a cellular “rheostat” to precisely control insulin secretion and suggest that disturbance of this control may contribute to beta cell dysfunction and type 2 diabetes. Targeting the microtubule regulation of insulin secretion may offer new ways to treat diabetes."
https://www.cell.com/developmental-cell/fulltext/S1534-5807(15)00554-7

Microtubuletes are potential anticancer drugs targets. So here mebendozole comes as low toxic and dirt cheap anticancer agent.

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells.
The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. - PubMed - NCBI

And it looks like mebendozole is able to lower intercellular stress responce.

Microtubules and Their Role in Cellular Stress in Cancer
Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule–protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.
Microtubules and Their Role in Cellular Stress in Cancer

Here comes more interesting conclusion that mebendozole is a KICKSTART for metabolic processes by turning off glycolysis.

Role of microtubules in the regulation of metabolism in isolated cerebral microvessels

We used 13C-labeled substrates and nuclear magnetic resonance spectroscopy to examine carbohydrate metabolism in vascular smooth muscle of freshly isolated pig cerebral microvessels (PCMV). PCMV utilized [2-13C]glucose mainly for glycolysis, producing [2-13C]lactate. Simultaneously, PCMV utilized the glycolytic intermediate [1-13C]fructose 1,6-bisphosphate (FBP) mainly for gluconeogenesis, producing [1-13C]glucose with only minor [3-13C]lactate production. The dissimilarity in metabolism of [2-13C]FBP derived from [2-13C]glucose breakdown and metabolism of exogenous [1-13C]FBP demonstrates that carbohydrate metabolism is compartmented in PCMV. Because glycolytic enzymes interact with microtubules, we disrupted microtubules with vinblastine. Vinblastine treatment significantly decreased [2-13C]lactate peak intensity (87.8 6 3.7% of control). The microtubule-stabilizing agent taxol also reduced [2-13C]lactate peak intensity (90.0 6 2.4% of control). Treatment with both agents further decreased [2-13C]lactate production (73.3 6 4.0% of control). Neither vinblastine, taxol, or the combined drugs affected [1-13C]glucose peak intensity (gluconeogenesis) or disrupted the compartmentation of carbohydrate metabolism. The similar effects of taxol and vinblastine, drugs that have opposite effects on microtubule assembly, suggest that they produce their effects on glycolytic rate by competing with glycolytic enzymes for binding, not by affecting the overall assembly state of the microtubule network. Glycolysis, but not gluconeogenesis, may be regulated in part by glycolytic enzyme-microtubule interactions.
We hypothesized that interactions between glycolytic enzymes and microtubules represent one structural basis for compartmentation of carbohydrate metabolism in VSM of pig cerebral microvessels (PCMV). To test this hypothesis, we examined the effects of both microtubule disruption and stabilization on glycolysis and gluconeogenesis in VSM of PCMV. Our results suggest that the binding of glycolytic enzymes to tubulin, rather than the integrity of the microtubule network, plays a significant role in the regulation of glycolytic flux. However, binding of gluconeogenic enzymes to tubulin does not contribute to the regulation of gluconeogenic flux. Thus these pathways may have spatially separate locations within the cytoplasm. The association of glycolytic enzymes with microtubules appears to have functional significance in terms of the regulation of pathway flux.
https://www.physiology.org/doi/pdf/10.1152/ajpcell.1999.277.6.c1250

Mebendozole is already under investigation as replacement for vincristine
Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors.
https://www.ncbi.nlm.nih.gov/pubmed/28386621

I bet mebendozole will disappear soon from OTC section. Now it is dirt cheap OTC at least in third-world countries.

 

[Makrosky]

I used mebendozole to reload my metabolism a couple of times. I found it's ability to reverse insulin resistance accidentally, I use it occasionally as antihelmitic drug as I live in third world with low hygienic standarts. First time I used it reversed my blood sugar issues completely in a matter of 2 days. Quick search "mebendozole insulin resistance" gives a proof.

Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies
https://link.springer.com/content/pdf/10.1007/BF00253502.pdf

Fasting plasma glucose concentrations in Type 1 diabetic patients were significantly reduced by I month of mebendazole therapy (12.83 +1.11 versus 6.56_+ 0.56 mmol/l; p< 0.05). These changes occurred despite reduced insulin doses in five out of six Type 1 diabetic patients (83_+ 32 versus 34_+ 8 units/day; NS). In the Type2 diabetic patients, similar decreases in fasting plasma glucose concentrations were observed (10.22_+ 0.56 versus 7.56 + 0.67 mmol/1; p < 0.05). Insulin doses were also reduced in four out of four Type 2 diabetic patients (69 + 23 versus 45 + 12 units/day; NS). Further, chlorpropamide was stopped in one and reduced in two Type 2 diabetic patients. Improvements in fasting plasma glucose concentrations cannot be attributed to weight reduction since four out of six Type 1 diabetic patients gained weight (78 + 12 versus 82 + 13 kg; NS) and two out of six Type 2 diabetic patients gained weight (107 _+ 9 versus 108 ___ 9 kg; NS).

In one presumed Type 1 diabetic patient, the fasting plasma glucose concentration approached normality, and his insulin doses were gradually and persistently decreased throughout a 5-month period after discontinuation of mebendazole. At that time insulin therapy was withdrawn and chlorpropamide therapy was started.


There are some other studies about hypoglycemic effects of mebendazole.

https://www.researchgate.net/public...nd_insulin_secretion_from_isolated_rat_islets
https://www.researchgate.net/public...ycemic_Potential_of_Benzimidazole_Derivatives

Mebendozole causes microtubules degeneration. And this is a way it works in glucose regulation disturbances.

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. - PubMed - NCBI

And microtubules act as a "a cellular “rheostat” to precisely control insulin secretion and suggest that disturbance of this control may contribute to beta cell dysfunction and type 2 diabetes. Targeting the microtubule regulation of insulin secretion may offer new ways to treat diabetes."
https://www.cell.com/developmental-cell/fulltext/S1534-5807(15)00554-7

Microtubuletes are potential anticancer drugs targets. So here mebendozole comes as low toxic and dirt cheap anticancer agent.

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells.
The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. - PubMed - NCBI

And it looks like mebendozole is able to lower intercellular stress responce.

Microtubules and Their Role in Cellular Stress in Cancer
Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule–protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.
Microtubules and Their Role in Cellular Stress in Cancer

Here comes more interesting conclusion that mebendozole is a KICKSTART for metabolic processes by turning off glycolysis.

Role of microtubules in the regulation of metabolism in isolated cerebral microvessels

We used 13C-labeled substrates and nuclear magnetic resonance spectroscopy to examine carbohydrate metabolism in vascular smooth muscle of freshly isolated pig cerebral microvessels (PCMV). PCMV utilized [2-13C]glucose mainly for glycolysis, producing [2-13C]lactate. Simultaneously, PCMV utilized the glycolytic intermediate [1-13C]fructose 1,6-bisphosphate (FBP) mainly for gluconeogenesis, producing [1-13C]glucose with only minor [3-13C]lactate production. The dissimilarity in metabolism of [2-13C]FBP derived from [2-13C]glucose breakdown and metabolism of exogenous [1-13C]FBP demonstrates that carbohydrate metabolism is compartmented in PCMV. Because glycolytic enzymes interact with microtubules, we disrupted microtubules with vinblastine. Vinblastine treatment significantly decreased [2-13C]lactate peak intensity (87.8 6 3.7% of control). The microtubule-stabilizing agent taxol also reduced [2-13C]lactate peak intensity (90.0 6 2.4% of control). Treatment with both agents further decreased [2-13C]lactate production (73.3 6 4.0% of control). Neither vinblastine, taxol, or the combined drugs affected [1-13C]glucose peak intensity (gluconeogenesis) or disrupted the compartmentation of carbohydrate metabolism. The similar effects of taxol and vinblastine, drugs that have opposite effects on microtubule assembly, suggest that they produce their effects on glycolytic rate by competing with glycolytic enzymes for binding, not by affecting the overall assembly state of the microtubule network. Glycolysis, but not gluconeogenesis, may be regulated in part by glycolytic enzyme-microtubule interactions.
We hypothesized that interactions between glycolytic enzymes and microtubules represent one structural basis for compartmentation of carbohydrate metabolism in VSM of pig cerebral microvessels (PCMV). To test this hypothesis, we examined the effects of both microtubule disruption and stabilization on glycolysis and gluconeogenesis in VSM of PCMV. Our results suggest that the binding of glycolytic enzymes to tubulin, rather than the integrity of the microtubule network, plays a significant role in the regulation of glycolytic flux. However, binding of gluconeogenic enzymes to tubulin does not contribute to the regulation of gluconeogenic flux. Thus these pathways may have spatially separate locations within the cytoplasm. The association of glycolytic enzymes with microtubules appears to have functional significance in terms of the regulation of pathway flux.
https://www.physiology.org/doi/pdf/10.1152/ajpcell.1999.277.6.c1250

Mebendozole is already under investigation as replacement for vincristine
Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors.
Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors. - PubMed - NCBI

I bet mebendozole will disappear soon from OTC section. Now it is dirt cheap OTC at least in third-world countries.

Do you think it's safe to take one single 500mg dose for parasite profilaxis?

 

[methylenewhite]

Safety of a New Chewable Formulation of Mebendazole for Preventive Chemotherapy Interventions to Treat Young Children in Countries with Moderate-to-High Prevalence of Soil Transmitted Helminth Infections
Safety of a New Chewable Formulation of Mebendazole for Preventive Chemotherapy Interventions to Treat Young Children in Countries with Moderate-to-High Prevalence of Soil Transmitted Helminth Infections

A single dose of mebendazole 500 mg chewable tablet was safe and well tolerated in children aged 2 to 10 years.

Looks like it is a safe pediatric dosage. Consult your doctor anyway before taking it.

 

[Makrosky]

Safety of a New Chewable Formulation of Mebendazole for Preventive Chemotherapy Interventions to Treat Young Children in Countries with Moderate-to-High Prevalence of Soil Transmitted Helminth Infections
Safety of a New Chewable Formulation of Mebendazole for Preventive Chemotherapy Interventions to Treat Young Children in Countries with Moderate-to-High Prevalence of Soil Transmitted Helminth Infections

A single dose of mebendazole 500 mg chewable tablet was safe and well tolerated in children aged 2 to 10 years.

Looks like it is a safe pediatric dosage. Consult your doctor anyway before taking it.

Ok thanks. Why should I consult my doctor though? I don't have access to any right now.

 

[Makrosky]

Now I'm reading the full study... "safe"... "Zanzibar".... LOL!!!!!!

 

[Sheila]

Thank you Mr Methylenwhite, this is most interesting.

Whilst repeat dosing is encouraged, the general 'first world' dose of mebendazole is 100mg adult or child (over 2 yrs) for helminths. These drugs are not without their risks but all is relative of course.

Some children do become what could be considered hypoglycaemic when taking this drug, but it is difficult to tease that possibility from a more generalised gut disturbance to worm removal. A 'good bowel clean out' will do the same, I thought that would be to do with (temporary) endotoxin reduction and cortisol reduction (both enabling oxidative metabolism once more). I have seen its presence or effect cause increased seizure activity in those susceptible.

Would not mebendazole delete tubules in the host as well as the cancerous tissue? Do we want it to do that - yes if it can be specific and cause apoptosis but not if it merely annoys the cancer cells further by starving them. This reminds me of how yeasts become more pathogenic on 'anti-candida' sugar reduction diets.

I really don't have a clear view here, but thank you, I find the whole world of anti-helminth strategies very interesting and note also how many of the Artemisia family have also been studied or used for their anti-cancer action. Artemisia sp. are essentially 'broad spectrum' too, with anti-microbial activity also but are not without their own set of potential risks.

It makes me wonder if mebendazole might have anti-microbial action also. Here: Mebendazole Is a Potential Alternative in the Treatment of Giardia duodenalis Infection it is used against protozoa. There may be more still.

Best wishes to you,

Sheila

 

[Memento]

User @Texon posted an interesting link to a cancer survivors blog in another thread: https://www.mycancerstory.rocks/sin...-your-life-how-to-change-your-own-perspective

Basically the guy had 3 months to live and is now 2 years cancer free because of Mebendazole! Theres also tens of other people that reportedly have succeeded with Mebendazole treatment in the same blog. Sounds pretty amazing for a dog worming med that costs a dime..

I bet mebendozole will disappear soon from OTC section. Now it is dirt cheap OTC at least in third-world countries.

From: Mebendazole - Wikipedia

Cost
In the developing world the wholesale cost is between 0.004 and 0.04 USD per dose as of 2014.[7] In the United States a single dose was about 18 USD in 2015.[3] In 2016 the price increased to 440.00 USD per dose in the U.S. as Amedra Pharmaceuticals acquired the rights from Teva in 2013.[8]

In 2010, Amedra also bought the U.S. marketing rights to the only other interchangeable anti-parasitic medication, albendazole, from GSK. The result of these acquisitions created a monopoly these medications and the price increased dramatically.[21]
​

So at least in US monopoly pricing is what they are going for.. Dirrty..





Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent

Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent

Abstract

Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix.

​

Authors propose many combinations with existing chemo drugs, antibiotics, cimetidine, metformin etc. because of low toxicity. There is a lot of interesting stuff in the article, I highly recommend reading it!

​

 

[Memento]

Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors

Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors

Abstract

The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.​

 

[Memento]

Anthelmintic mebendazole enhances cisplatin's effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC)

Anthelmintic mebendazole enhances cisplatin's effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC)

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells. MBZ effectively inhibits cell proliferation, cell cycle progression and cell migration, and induces apoptosis of HNSCC cells. Mechanistically, MBZ can modulate the cancer-associated pathways including ELK1/SRF, AP1, STAT1/2, MYC/MAX, although the regulatory outcomes are context-dependent. MBZ also synergizes with cisplatin in suppressing cell proliferation and inducing apoptosis of human HNSCC cells. Furthermore, MBZ is shown to promote the terminal differentiation of CAL27 cells and keratinization of CAL27-derived xenograft tumors. Our results are the first to demonstrate that MBZ may exert its anticancer activity by inhibiting proliferation while promoting differentiation of certain HNSCC cancer cells. It's conceivable the anthelmintic drug MBZ can be repurposed as a safe and effective agent used in combination with other frontline chemotherapy drugs such as cisplatin in HNSCC treatment.​

 

[danishispsychic]

And no one believed Hulda Clark about the parasite/ cancer connection.....

 

[Waynish]

Who knows how it is synthesized?

 

[Texon]

User @Texon posted an interesting link to a cancer survivors blog in another thread: https://www.mycancerstory.rocks/sin...-your-life-how-to-change-your-own-perspective

Basically the guy had 3 months to live and is now 2 years cancer free because of Mebendazole! Theres also tens of other people that reportedly have succeeded with Mebendazole treatment in the same blog. Sounds pretty amazing for a dog worming med that costs a dime..




From: Mebendazole - Wikipedia

Cost
In the developing world the wholesale cost is between 0.004 and 0.04 USD per dose as of 2014.[7] In the United States a single dose was about 18 USD in 2015.[3] In 2016 the price increased to 440.00 USD per dose in the U.S. as Amedra Pharmaceuticals acquired the rights from Teva in 2013.[8]

In 2010, Amedra also bought the U.S. marketing rights to the only other interchangeable anti-parasitic medication, albendazole, from GSK. The result of these acquisitions created a monopoly these medications and the price increased dramatically.[21]
​

So at least in US monopoly pricing is what they are going for.. Dirrty..





Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent

Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent

Abstract

Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix.

​

Authors propose many combinations with existing chemo drugs, antibiotics, cimetidine, metformin etc. because of low toxicity. There is a lot of interesting stuff in the article, I highly recommend reading it!

​

Actually he is taking Fenbenzadole. I have not seen him mention MZ though.

 

[Memento]

Oh crap, sorry for mixing them up then. Seems that most of the anti helmintic benzimidazoles have anti cancer activity. MBZ has just more research behind it.

 

[methylenewhite]

And no one believed Hulda Clark about the parasite/ cancer connection.....

There is no connection. It is just shared target mechanism that many types of cells of different organisms have.

 

[Frankdee20]

Would'nt taking this without confirmed infestation create resistance ? That is why I never agreed with some on here who do low dose Antibiotics. For me, Tinidazole and Paramomycin had zero side effects when I was dealing with something. Metronidazole was so powerful though, in the sense that I did feel the blood sugar lowering effects and it made me crazily agitated.

 

[Memento]

Microtubule depolymerizing, anti-angiogenic, increased p53 expression and what else..

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells


Abstract

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.



​

The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation. - PubMed - NCBI

Abstract

Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1β and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1β secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1β release. MBZ-induced IL-1β release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
​

WBC activation is good, right?

​

 

[danishispsychic]

There is no connection. It is just shared target mechanism that many types of cells of different organisms have.

can you post a study? super interested

 

[methylenewhite]

Would'nt taking this without confirmed infestation create resistance ? That is why I never agreed with some on here who do low dose Antibiotics. For me, Tinidazole and Paramomycin had zero side effects when I was dealing with something. Metronidazole was so powerful though, in the sense that I did feel the blood sugar lowering effects and it made me crazily agitated.

BZ resistance is very common but if there is no infestation it should not create resistance because there are no "worms" to evolve and become resistance. Antibiotics resistance is different. You use wide spectrum AB and attack almost all inhabitants in case of bacteria. In helmints its different, there is usually only 1-2-3 types of "amigos" residing in someones gut. And they could become resistant.

 

[methylenewhite]

can you post a study? super interested

Read carefully all the link I posted in the first message. Its all explained there. Tubulin in microtubules is the target.
In case you dont have much time to read all this link is for you Microtubule#Tubulin-binding_drugs_and_chemical_effects

 

[greengr]

Any news on this?