Dr. Weeks’ Comment: As part of my Corrective Cancer Care™,  I have prescribed chemotherapy drugs to patients with cancer in the context of insulin potentiation for decades and found it highly beneficial. However, even low dose insulin potentiated chemotherapy is suboptimal compared to immune enhancement (“teach a man to fish”) and optimizing lifestyle (epigenetic) factors using diet to reduce inflammation and exercise to optimize oxygenation of tissues.  Meanwhile, farmers I know deworm their livestock at least yearly, but has your doctor suggested deworming you? No? Why not? You DO love sushi… after all, don’t you? (I do.)

Enter the remarkable news about anti-parasite drugs and their potential role in helping your immune system beat cancer.

Warning: I do not endorse humans using veterinary products. Share this info with your doctors.

How might these agents fight cancer? What might the scientific rationale be for incorporating these inexpensive agents?

Well, anti-parasite drugs work by targeting a cellular structure necessary for cellular replication: microtubules.  Interested?

3 pathways mechanisms of actions

• destroys the microtubules in cancer cell wall so no cellular replication
• interrupts cancer cells ability to metabolize sugar
• increases level of P53 tumor suppressor gene

Read on..

The role of microtubule targeting in cancer therapy

per ChatGPT on 8-1-24

“Microtubule targeting plays a crucial role in cancer therapy due to the essential functions of microtubules in cell division. Here’s a detailed overview:

Overview of Microtubules

Microtubules are part of the cytoskeleton of the cell, providing structural support and playing a key role in various cellular processes, including intracellular transport, cell shape maintenance, and most importantly, cell division (mitosis). They are dynamic structures composed of tubulin protein subunits.

Mechanism of Action in Cancer Therapy

Cancer cells are characterized by uncontrolled division and growth. Microtubule-targeting agents (MTAs) disrupt microtubule dynamics, interfering with mitosis and leading to cell death (apoptosis). MTAs can be broadly categorized into two main types:

1. Microtubule-Disrupting Agents
   • Examples: Vincristine, Vinblastine
   • Mechanism: These agents bind to tubulin and inhibit its polymerization into microtubules, preventing the formation of the mitotic spindle necessary for chromosome segregation during mitosis.
2. Microtubule-Stabilizing Agents
   • Examples: Paclitaxel (Taxol), Docetaxel
   • Mechanism: These agents stabilize microtubules, preventing their depolymerization. This stabilization leads to the formation of abnormally stable and dysfunctional microtubules, which also interferes with mitosis.

Specific Drugs and Their Impact

1. Paclitaxel (Taxol)
   • Source: Originally derived from the bark of the Pacific yew tree.
   • Use: Widely used to treat various cancers, including ovarian, breast, and non-small cell lung cancer.
   • Mechanism: Promotes microtubule polymerization and stabilization, causing cell cycle arrest at the G2/M phase and leading to apoptosis.
2. Vincristine
   • Source: Derived from the periwinkle plant.
   • Use: Used to treat leukemia, lymphoma, and some solid tumors.
   • Mechanism: Binds to tubulin and inhibits microtubule formation, preventing cell division.
3. Docetaxel
   • Use: Similar to Paclitaxel, used in breast, prostate, and lung cancer.
   • Mechanism: Stabilizes microtubules and inhibits their disassembly, disrupting mitosis.

Clinical Implications and Side Effects

While effective, MTAs come with a range of side effects primarily due to their impact on normal, rapidly dividing cells (e.g., bone marrow cells, hair follicles, gastrointestinal tract cells). Common side effects include:

• Neuropathy (nerve damage)
• Myelosuppression (decreased bone marrow activity)
• Alopecia (hair loss)
• Gastrointestinal disturbances

Resistance to Microtubule-Targeting Agents

Cancer cells can develop resistance to MTAs through various mechanisms, such as:

• Drug Efflux: Overexpression of drug transporters (e.g., P-glycoprotein) that pump the drug out of the cells.
• Tubulin Mutations: Changes in tubulin structure that reduce drug binding.
• Microtubule-Associated Proteins (MAPs): Alterations in proteins that interact with microtubules, affecting drug sensitivity.

Future Directions

Research is ongoing to develop new MTAs with improved efficacy and reduced side effects, as well as to overcome resistance mechanisms. Strategies include:

• Nanoparticle-Based Delivery: Enhancing drug delivery specifically to cancer cells, minimizing impact on normal cells.
• Combination Therapies: Using MTAs in combination with other anticancer agents to enhance effectiveness and reduce resistance.”

Now let’s look more closely at Ivermectin, Fenbendazole and Albendazole for prostate cancer in particular:

IVERMECTIN

Cell Death Dis. 2022 Sep 1;13(9):754.

doi: 10.1038/s41419-022-05182-0.

Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer

Shidong Lv ^# 1 2, Zeyu Wu ^# 2 3, Mayao Luo ¹, Yifan Zhang ¹, Jianqiang Zhang ^1 4, Laura E Pascal ^2 5, Zhou Wang ^6 7 8, Qiang Wei ⁹

Abstract

Ivermectin is a widely used antiparasitic drug and shows promising anticancer activity in various cancer types. Although multiple signaling pathways modulated by ivermectin have been identified in tumor cells, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and targets of ivermectin in prostate cancer. Ivermectin caused G0/G1 cell cycle arrest, induced cell apoptosis and DNA damage, and decreased androgen receptor (AR) signaling in prostate cancer cells. Further in vivo analysis showed ivermectin could suppress 22RV1 xenograft progression. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were strongly suggested as direct targets of ivermectin in prostate cancer. The interaction of ivermectin and FOXA1 reduced the chromatin accessibility of AR signaling and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The interaction of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair ability after AR signaling inhibition, ivermectin increased intracellular DNA double-strand breaks and finally triggered cell death. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for prostate cancer.

~~~

J Exp Clin Cancer Res. 2019 Jun 18;38(1):265.

doi: 10.1186/s13046-019-1251-7.

Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway

Lu Jiang ^1 2, Pan Wang ¹, Ying-Jian Sun ^3 4, Yi-Jun Wu ⁵

Abstract

Background: Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs.

Results: Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-κB. The inhibition of the transcriptional factor NF-κB led to the reduced P-gp transcription.

Conclusions: These findings demonstrated that ivermectin significantly enhanced the anti-cancer efficacy of chemotherapeutic drugs to tumor cells, especially in the drug-resistant cells. Thus, ivermectin, a FDA-approved antiparasitic drug, could potentially be used in combination with chemotherapeutic agents to treat cancers and in particular, the drug-resistant cancers.

~~~

Anticancer Agents Med Chem. 2024;24(5):348-357.

doi: 10.2174/0118715206274095231106042833.

Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage

Ning Fan ¹, Lixiu Zhang ², Zhiping Wang ¹, Hui Ding ¹, Zhongjin Yue ¹

Abstract

Background: Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer.

Objectives: To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells in vitro and in vivo.

Methods: CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin in vivo.

Results: Our study showed that in vitro and in vivo, Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathway related proteins in bladder cancer cells.

Conclusions: According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.

~~~

NPJ Breast Cancer. 2021 Mar 2;7(1):22.

doi: 10.1038/s41523-021-00229-5.

Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer

Dobrin Draganov ¹, Zhen Han ¹, Aamir Rana ¹, Nitasha Bennett ², Darrell J Irvine ^2 3, Peter P Lee ⁴

Abstract

We show that treatment with the FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis which operates in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio. While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p = 0.03) and promoted complete responses (p < 0.01), also leading to immunity against contralateral re-challenge with demonstrated anti-tumor immune responses. Going beyond primary tumors, this combination achieved significant reduction in relapse after neoadjuvant (p = 0.03) and adjuvant treatment (p < 0.001), and potential cures in metastatic disease (p < 0.001). Statistical modeling confirmed bona fide synergistic activity in both the adjuvant (p = 0.007) and metastatic settings (p < 0.001). Ivermectin has dual immunomodulatory and ICD-inducing effects in breast cancer, converting cold tumors hot, thus represents a rational mechanistic partner with checkpoint blockade.

~~~

~~~

FENBENDAZOLE

Front Oncol. 2021 Mar 2:10:594141.

doi: 10.3389/fonc.2020.594141. eCollection 2020.

Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer

Ivy Chung ^1 2, Kun Zhou ^1 2, Courtney Barrows ¹, Jacqueline Banyard ^1 2, Arianne Wilson ¹, Nathan Rummel ³, Atsushi Mizokami ⁴, Sudipta Basu ⁵, Poulomi Sengupta ⁵, Badaruddin Shaikh ³, Shiladitya Sengupta ⁵, Diane R Bielenberg ^1 2, Bruce R Zetter ^1 2

Abstract

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients’ prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases – two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

~~~~

Pharmaceutics. 2021 Oct 2;13(10):1605.

doi: 10.3390/pharmaceutics13101605.

PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells

Maedeh Koohi Moftakhari Esfahani ^1 2, Seyed Ebrahim Alavi ³, Peter J Cabot ⁴, Nazrul Islam ⁵, Emad L Izake ^1 2

Abstract

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

~~~

Case Report, Clin Oncol Case Rep Vol: 4 Issue: 2

Fenbendazole Enhancing Anti-Tumor Effect: A Case Series

Ryan S Chiang^1*, Ali B Syed², Jonathan L Wright³, Bruce Montgomery³ and Sandy Srinivas⁴

Abstract

AND

ALBENDAZOLE

Mol Ther Oncol. 2024 May 6;32(2):200813.

doi: 10.1016/j.omton.2024.200813. eCollection 2024 Jun 20.

Enhancing antitumor efficacy of oncolytic virus M1 via albendazole-sustained CD8⁺ T cell activation

Wenjing Bai ^1 2, Xia Tang ^1 2, Tong Xiao ^1 2, Yangyang Qiao ^1 2, Xuyan Tian ^1 2, Bo Zhu ^1 2, Jiehong Chen ¹, Chaoxin Chen ¹, Yuanyuan Li ¹, Xueying Lin ^1 2, Jing Cai ^1 3, Yuan Lin ¹, Wenbo Zhu ¹, Guangmei Yan ^1 4, Jiankai Liang ^1 2, Jun Hu ^1 2

Abstract

The immune response plays a crucial role in the functionality of oncolytic viruses. In this study, Albendazole, an antihelminthic drug known to modulate the immune checkpoint PD-L1, was combined with the oncolytic virus M1 (OVM1) to treat mice with either prostate cancer (RM-1) or glioma (GL261) tumors. This combination therapy enhanced anti-tumor effects in immunocompetent mice, but not in immunodeficient ones, without increasing OVM1 replication. Instead, it led to an increase in the number of CD8⁺ T cells within the tumor, downregulated the expression of PD1 on CD8⁺ T cells, and upregulated activation markers such as Ki67, CD44, and CD69 and the secretion of cytotoxic factors including interferon (IFN)-γ, granzyme B, and tumor necrosis factor (TNF)-α. Consistently, it enhanced the in vitro tumor-killing activity of lymphocytes from tumor-draining lymph nodes or spleens. The synergistic effect of Albendazole on OVM1 was abolished by depleting CD8⁺ T cells, suggesting a CD8⁺ T cell-dependent mechanism. In addition, Albendazole and OVM1 therapy increased CTLA4 expression in the spleen, and the addition of CTLA4 antibodies further enhanced the anti-tumor efficacy in vivo. In summary, Albendazole can act synergistically with oncolytic viruses via CD8⁺ T cell activation, and the Albendazole/OVM1 combination can overcome resistance to CTLA4-based immune checkpoint blockade therapy.

Korean J Parasitol. 2021 Jun;59(3):189-225.

doi: 10.3347/kjp.2021.59.3.189. Epub 2021 Jun 21.

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

Jong-Yil Chai ^1 2, Bong-Kwang Jung ¹, Sung-Jong Hong ³

Abstract

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

 ~~~~

Oncol Lett. 2021 May;21(5):395.

doi: 10.3892/ol.2021.12656. Epub 2021 Mar 18.

Albendazole exerts antiproliferative effects on prostate cancer cells by inducing reactive oxygen species generation

Ukjin Kim ¹, Changsoo Shin ², C-Yoon Kim ³, Bokyeong Ryu ¹, Jin Kim ¹, Junpil Bang ¹, Jae-Hak Park ¹

Abstract

Benzimidazole derivatives are used for their antihelmintic properties, but have also been reported to exert anticancer effects. In the present study, the anticancer effects of albendazole on prostate cancer cells were assessed using proliferation, clonogenic and migration assays. To investigate the anticancer mechanisms of albendazole, reactive oxygen species (ROS) levels were measured, and the expression of genes associated with oxidative stress and Wnt/β-catenin signaling was confirmed by reverse transcription-quantitative PCR and western blotting. Albendazole selectively inhibited the proliferation of the PC3, DU145, LNCaP and AT2 prostate cancer cell lines at concentrations that did not affect the proliferation of a normal prostate cell line (RWPE-1). Albendazole also inhibited the colony formation and migration of PC3 and DU145 cells, as well as inducing ROS production. Diphenyleneiodonium chloride, an inhibitor of NADPH oxidase (NOX), one of the sources of ROS, decreased basal ROS levels in the PC3 and DU145 cells, but did not reduce albendazole-associated ROS production, suggesting that ROS production following albendazole treatment was NOX-independent. The anticancer effect was decreased when albendazole-induced ROS was reduced by treatment with antioxidants (glutathione and N-acetylcysteine). Furthermore, albendazole decreased the mRNA expression of CDGSH iron sulfur domain 2, which regulates antioxidant activity against ROS, as well as the antioxidant enzymes catalase, and glutathione peroxidase 1 and 3. Albendazole also decreased the mRNA expression of catenin β1 and transcription factor 4, which regulate Wnt/β-catenin signaling and its associated targets, Twist family BHLH transcription factor 1 and BCL2. The albendazole-related decrease in the expression levels of oxidative stress-related genes and Wnt/β-catenin signaling proteins was thought to be associated with ROS production. These results suggest that the antihelmintic drug, albendazole, has inhibitory effects against prostate cancer cells in vitro. Therefore, albendazole may potentially be used as a novel anticancer agent for prostate cancer.

~~~~

Front Oncol. 2021 Mar 2:10:594141.

doi: 10.3389/fonc.2020.594141. eCollection 2020.

Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer

Ivy Chung ^1 2, Kun Zhou ^1 2, Courtney Barrows ¹, Jacqueline Banyard ^1 2, Arianne Wilson ¹, Nathan Rummel ³, Atsushi Mizokami ⁴, Sudipta Basu ⁵, Poulomi Sengupta ⁵, Badaruddin Shaikh ³, Shiladitya Sengupta ⁵, Diane R Bielenberg ^1 2, Bruce R Zetter ^1 2

Abstract

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients’ prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases – two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

~~~~

Oncotarget. 2017 Apr 20;8(42):71512-71519.

doi: 10.18632/oncotarget.17292. eCollection 2017 Sep 22.

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer

Farhad Ghasemi ¹, Morgan Black ^1 2, Frederick Vizeacoumar ³, Nicole Pinto ^1 2, Kara M Ruicci ^1 2, Carson Cao Son Huu Le ^4 5, Matthew R Lowerison ^6 7, Hon Sing Leong ^4 5, John Yoo ^1 2, Kevin Fung ^1 2, Danielle MacNeil ^1 2, David A Palma ², Eric Winquist ², Joe S Mymryk ^1 2 8, Paul C Boutros ^9 10, Alessandro Datti ³, John W Barrett ^1 2, Anthony C Nichols ^1 2

Abstract

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC₅₀ of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer.

~~~~

Exp Ther Med. 2017 Feb;13(2):595-603.

doi: 10.3892/etm.2016.3992. Epub 2016 Dec 22.

Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis

Xuan Zhang ¹, Jing Zhao ², Xiangyang Gao ², Dongsheng Pei ³, Chao Gao ²

Retraction in

• [Retracted] Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis.

Zhang X, Zhao J, Gao X, Pei D, Gao C.Exp Ther Med. 2024 Mar 26;27(5):227. doi: 10.3892/etm.2024.12513. eCollection 2024 May.PMID: 38596655 Free PMC article.

Abstract

As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis.

~~~ 

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

BONUS

re Fenbendazole  https://rumble.com/v3q04y6-joe-tippens-fenbendazole-cancer.html

Good for you to have read this far.

Your reward is this fine video on science and medicine. Start at minute 44…