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The Korean Journal of Parasitology Jun 2021The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed.... (Review)
Review
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.
Topics: Albendazole; Animals; Anthelmintics; Antineoplastic Agents; Ascariasis; Female; Humans; Male; Mebendazole; Parasites; Trichuriasis
PubMed: 34218593
DOI: 10.3347/kjp.2021.59.3.189 -
American Family Physician Mar 2004Intestinal parasites cause significant morbidity and mortality. Diseases caused by Enterobius vermicularis, Giardia lamblia, Ancylostoma duodenale, Necator americanus,... (Review)
Review
Intestinal parasites cause significant morbidity and mortality. Diseases caused by Enterobius vermicularis, Giardia lamblia, Ancylostoma duodenale, Necator americanus, and Entamoeba histolytica occur in the United States. E. vermicularis, or pinworm, causes irritation and sleep disturbances. Diagnosis can be made using the "cellophane tape test." Treatment includes mebendazole and household sanitation. Giardia causes nausea, vomiting, malabsorption, diarrhea, and weight loss. Stool ova and parasite studies are diagnostic. Treatment includes metronidazole. Sewage treatment, proper handwashing, and consumption of bottled water can be preventive. A. duodenale and N. americanus are hookworms that cause blood loss, anemia, pica, and wasting. Finding eggs in the feces is diagnostic. Treatments include albendazole, mebendazole, pyrantel pamoate, iron supplementation, and blood transfusion. Preventive measures include wearing shoes and treating sewage. E. histolytica can cause intestinal ulcerations, bloody diarrhea, weight loss, fever, gastrointestinal obstruction, and peritonitis. Amebas can cause abscesses in the liver that may rupture into the pleural space, peritoneum, or pericardium. Stool and serologic assays, biopsy, barium studies, and liver imaging have diagnostic merit. Therapy includes luminal and tissue amebicides to attack both life-cycle stages. Metronidazole, chloroquine, and aspiration are treatments for liver abscess. Careful sanitation and use of peeled foods and bottled water are preventive.
Topics: Adult; Amebicides; Ancylostoma; Animals; Child; Entamoeba histolytica; Entamoebiasis; Enterobiasis; Enterobius; Giardia lamblia; Giardiasis; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Necator americanus
PubMed: 15023017
DOI: No ID Found -
International Journal of Molecular... Jan 2023Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical... (Review)
Review
Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood-brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.
Topics: Male; Animals; Mebendazole; Antiparasitic Agents; Cell Line, Tumor; Hedgehog Proteins; Antineoplastic Agents; Brain Neoplasms; Head and Neck Neoplasms; Anti-Infective Agents; Glioma
PubMed: 36674870
DOI: 10.3390/ijms24021334 -
Immunity Apr 2022The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines,...
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.
Topics: Acylation; Alarmins; Anthelmintics; Biomarkers, Tumor; Cytokines; DNA-Binding Proteins; Helminthiasis; Humans; Hyperplasia; Inflammation; Interleukin-33; Intestinal Mucosa; Mebendazole; N-Acetylglucosaminyltransferases; Pore Forming Cytotoxic Proteins; STAT6 Transcription Factor
PubMed: 35385697
DOI: 10.1016/j.immuni.2022.03.009 -
Gynecologic Oncology Jan 2021Mebendazole and other anti-parasitic drugs are being used off-prescription based on social media and unofficial accounts of their anti-cancer activity. The purpose of...
OBJECTIVE
Mebendazole and other anti-parasitic drugs are being used off-prescription based on social media and unofficial accounts of their anti-cancer activity. The purpose of this study was to conduct a controlled evaluation of mebendazole's therapeutic efficacy in cell culture and in vivo models of ovarian cancer. The majority of ovarian cancers harbor p53 null or missense mutations, therefore the effects of p53 mutations and a mutant p53 reactivator, PRIMA-1 (APR246) on mebendazole activity were evaluated.
METHODS
Mebendazole was evaluated in cisplatin-resistant high grade serous stage 3C ovarian cancer patient derived xenograft (PDX) models: PDX-0003 (p53 null) and PDX-0030 (p53 positive), and on ovarian cancer cell lines: MES-OV (p53 R282W), ES2 (p53 S241F), A2780 (p53 wild type), SKOV3 parental (p53 null) and isogenic sublines, SKOV3 R273H p53 and SKOV3 R248W p53. Drug synergy and mechanisms were evaluated in cell cultures using isobolograms, clonogenic assays and western blots. Prevention of tumor establishment was studied in a MES-OV orthotopic model.
RESULTS
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-1 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.
CONCLUSION
This work demonstrates the therapeutic potential of repurposing mebendazole and supports clinical development of mebendazole for ovarian cancer therapy and maintenance.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Drug Repositioning; Drug Screening Assays, Antitumor; Drug Synergism; Female; Fenbendazole; Humans; Mebendazole; Ovarian Neoplasms; Quinuclidines; Random Allocation; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays
PubMed: 33131904
DOI: 10.1016/j.ygyno.2020.10.010 -
Open Access Macedonian Journal of... Apr 2019Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of...
BACKGROUND
Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of helminthiasis in children.
AIM
To investigated the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis and ascariasis.
METHODS
This study was conducted as a double-blind, randomised clinical trial by comparing the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis. The sample of this study were 180 elementary school students at Deli Serdang Regency State Elementary School, Medan, Indonesia. The study was conducted from April to June 2015.
RESULT
The cure rate of helminthiasis on the 7th day was 81.7% after albendazole therapy, 88.3% after albendazole levamisole therapy, and 83.3% after mebendazole combined with levamisole therapy (p = 0.577). Cure rate on the 14th day was 88.3%, 95%, and 91.7% for albendazole, albendazole combined with levamisole, and mebendazole combined with levamisole therapy, respectively (p = 0.418). On the 21th day, the cure rate was 88.3%, 96.7%, and 91.7% (p = 0.230). Combination of albendazole and levamisole showed the highest cure rate, despite the statistically insignificant difference for all groups (p > 0.05). Combination of albendazole combined with levamisole showed better cure rate for mild trichuriasis (95.8%) than albendazole therapy (46.2%) and mebendazole combined with levamisole (83.3%), (p < 0.05).
CONCLUSION
Single-dose albendazole, a combination of albendazole and levamisole, and a combination of mebendazole and levamisole had similar efficacy in reducing egg count in helminthiasis. Combination of albendazole and levamisole showed better cure rate for mild trichuriasis and mixed infections. Side effects were similar in all treatment groups.
PubMed: 31110573
DOI: 10.3889/oamjms.2019.299