mebendazole lung cancer

One day later, all animals received an injection of 2 × 106 H460 tumor cells into the lower right flank. Next, DNA fragments were precipitated with 0.5 m NaCl and 50% isopropanol, and the samples were loaded in 2% agarose TBE gel and stained with ethidium bromide. , 2) Inhibition of MAPK/ERK pathway, induction of apoptosis, synergy with trametinib, Human head and neck squamous cell carcinoma CAL27 and SCC15, Apoptosis induction as a single drug. D, tumors were excised from control and MZ-treated nu/nu mice after 4 weeks and photographed. However, the results of crystallographic and other studies have indicated that the tubulin-binding site of BZs is distinctly different from that of other microtubule-disrupting agents such as vinblastine and paclitaxel. 1C⇓ We do not retain these email addresses. Tan, Z.; Chen, L.; Zhang, S. Comprehensive Modeling and Discovery of Mebendazole as a Novel TRAF2- and NCK interacting Kinase Inhibitor. ; Staedtke, V.; Wanjiku, T.; Rudek, M.A. Lung cancer has become the leading cause of cancer death in the world (1). ; Byers, S.W. Nygren, P.; Larsson, R. Drug repositioning from bench to bedside: Tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer. The compounds known as BZs3 Drugs in the latter group bind to tubulin at sites located near the intradimer interface and facing the lumen of the microtubule, whereas the possible binding site for BZs is on the outside of the microtubule (25 Thin arrows, apoptotic nuclei; thick arrows, mitotic nuclei. Fenbendazole inhibits the cellular proteasome function dose- and time-dependently and leads to accumulation of ubiquitylated derivatives of various cellular proteins, including p53, which, in turn, leads to apoptosis via the mitochondrial pathway Pinto, L.C. To summarize the study results, we reported descriptive statistics such as the mean and SD. In this study, MZ arrested cells at the G 2 -M phase before the onset of apoptosis, as detected by using fluorescence-activated cell sorter analysis. Microtubules serve as an intracellular scaffold, and their unique polymerization dynamics are critical for many cellular functions (1 Chico, L.K. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme. C, dose-dependent DNA fragmentation analysis was done in H460 cells after 24 h of MZ treatment. The costs of publication of this article were defrayed in part by the payment of page charges. We found a marked difference in tumor weight between the MZ-treated and control animals (Fig. Expression of p53 and p21 proteins was induced after 24 h and after 48 h cell apoptosis (mediated by both cytochrome c and caspases) was reported. The molecular mechanisms of chemoresistance in cancers. Bai, R.Y. ; Joe, Y.A. Immunoreactive proteins were detected using enhanced chemiluminescence (Amersham). ; Gilbertson, R.J.; Cho, Y.J. Bars, SE. Targeting acute myeloid leukemia by drug-induced c-MYB degradation. For example, rapid, extensive metabolism of BZs into less toxic metabolites (e.g., sulfoxides and sulfones) by the hepatic microsomal enzymes (28 2G)⇓ H460 cells were injected into mice (2 × 106 cells/mouse), and mice having established tumors (3–4 mm in diameter) were fed different concentrations of MZ (T02, T04, and T08, 200, 400, and 800 μg of MZ, respectively) every other day, whereas control animals received PBS. Williamson, T.; Bai, R.Y. Furthermore, disruption of the equilibrium between tubulin monomers/dimers and microtubule polymers using microtubule-stabilizing (e.g., paclitaxel, docetaxel) or microtubule-destabilizing (e.g., vinblastine, vincristine, nocodazole, colchicine) agents activates the stress-activated protein kinase signaling cascade. Braithwaite, P.A. Mebendazole-induced M1 polarization of THP-1 macrophages may involve DYRK1B inhibition. . by photographing the area of s.c. neovascularization in mice overlying a semipermeable membrane chamber containing H460 or A549 cells. Central to the success of the BZs is their selective toxicity in helminths. We have found that mebendazole (MZ), a derivative of benzimidazole, induces a dose- and time-dependent apoptotic response in human lung cancer cell lines. Hedgehog ligands or markers of downstream pathway activity have been detected in melanomas, lung cancers, ovarian cancers, adrenocortical cancers and colorectal cancers (Ref. From the next day onward after implantation, the mice were given an oral suspension of MZ (1 mg/mouse/day); five mice were used in each group. Given the low toxicity and published anticancer mechanisms of mebendazole, this novel preclinical study of mebendazole in thyroid cancer has promising therapeutic implications for patients with treatment refractory papillary or anaplastic thyroid cancer. [, Recent studies suggest that microtubule inhibitors synergize with ionizing radiations (IRs) not only during mitosis, but also during interphase [, In a paper published in 2008, Martarelli et al. ; Martin, S.; Kerr, R.; Harbottle, A.; Lovat, P.E. ; Neto, E.P. Corti, N.; Heck, A.; Rentsch, K.; Zingg, W.; Jetter, A.; Stieger, B.; Pauli-Magnus, C. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: An interaction study in healthy volunteers. . 0.5 µM tubulin depolymerization. Jornet, D.; Bosca, F.; Andreu, J.M. + metformin up to 1000 mg b.i.d. Other cell lines: 0.1–0.8 μM. 2I)⇓ TAMeless traitors: Macrophages in cancer progression and metastasis. are also known to bind microtubules, but their effect on tumor cells has remained elusive. To exclude the possibility that the reduced vasculature was attributable to a lack of viable tumor cells in the chamber, we prelabeled tumor cells using a fluorescent dye before injecting them into the chamber. ; Tabassum, R.; Hussain, Z.; Baba, A.A.; Lone, R.A. Albendazole as an adjuvant to the standard surgical management of hydatid cyst liver. Subdiploid populations indicate the apoptotic cells. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. It is conceivable that cytoskeletal dysfunction, manifested as either a disrupted microtubule network or stabilized, “rigid” microtubule cytoskeleton, is an intracellular stress. It should be noted that the control implant had a tree-like architecture of major vessels (arrow) connecting to minor branches but that the MZ-treated implants had scarce vessels. ; Abdussamad, M.; Zhou, H.; Zapas, J.; Calvert, V.; Petricoin, E.F.; et al. Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both in Vitro and in Vivo1 Tapas Mukhopadhyay,2 Ji-ichiro Sasaki, Rajagopal Ramesh, and Jack A. Roth ... that mebendazole (MZ), a derivative of benzimidazole, induces a dose- and time-dependent apo-ptotic response in human lung cancer cell lines. Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo. ; Confortin, G.; Junqueira, A.V. ; Madhavan, S.; Uren, A.; Brown, M.L. In this study, MZ arrested cells at the G2-M phase before the onset of … Five-μm sections of paraffin-embedded tissue samples were stained with H&E and subjected to immunoperoxidase detection of endothelial cells using a CD31 antibody (18) every other day for a total of three treatments. Add resources to your list by clicking the checkbox next to the title. Of these mechanisms, fumarate reductase, glucose uptake, and microtubule inhibition satisfy many of the criteria considered relevant for a putative site of action. ; Szwajcer, M.; Chin, M.; Liauw, W.; Seef, J.; Galettis, P.; Morris, D.L. The associated drugs include albendazole, thiabendazole, riclabendazole, flubendazole, mebendazole and fenbendazole. . ; Springer, C.J. , 24) to nu/nu mice, MZ strongly inhibited the growth of human tumor xenografts and significantly reduced the number and size of tumors in an experimental model of lung metastasis. Lung cancer. Searching the medical database PubMed for "Mebendazole cancer", one finds papers such as Potential anti-cancer drugs commonly used for other indications, Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors, Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo, "Revisiting Non-Cancer Drugs for Cancer Therapy" … H460 tumors were then harvested, photographed (Fig. In all of the staining procedures, we included appropriate negative controls. In our dorsal air sac study, when sacs containing the tumor cells were further stained with Hoechst 33258 and observed under a fluorescence microscope, a significant number of cells showed apoptotic nuclei and DNA fragmentation (data not shown), which supports our in vitro data and may contribute to reduced vessel formation. When administered p.o. This tumor-suppressing effect of MZ may have been attributable to inhibition of tumor-induced angiogenesis. Buttrick, S.; Shah, A.H.; Komotar, R.J.; Ivan, M.E. Cancer stem cells and chemoresistance: The smartest survives the raid. Cells were rounded and partly detached after 12 h of MZ treatment. These results suggest that MZ is effective in the treatment of cancer and other angiogenesis-dependent diseases. No effect on HUVECs and normal fibroblasts also at 1 μM. Angiogenesis inhibition Metastatic spread inhibition. Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism. ; Burbano, R.M. ; Soares, B.M. Targeting Cancer Stemness in the Clinic: From Hype to Hope. ISSN: 1078-0432, Sign In to Email Alerts with your Email Address. Plasma concentrations of mebendazole during treatment of echinococcosis: Preliminary results. Human colon cancer cell lines HT29, HCT-8 and SW626, HCT 116 and RKO, Less than 5 μM for all the lines tested and <1 μM for 3 lines. Yeldag, G.; Rice, A.; Del Río Hernández, A. Chemoresistance and the Self-Maintaining Tumor Microenvironment. Also, BZs have been reported to have poor systemic absorption after oral administration in vivo. Disruption of microtubules, inhibition of invasion and migration and of MMP-2 activity. Poruchynsky, M.; Komlodi-Pasztor, E.; Trostel, S.; Wilkerson, J.; Regairaz, M.; Pommier, Y.; Zhang, X.; Kumar, M.T. Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells. The experiments were performed three times, and data were analyzed and interpreted as being statistically significant if P < 0.05, according to the Mann-Whitney test. Thank you for sharing this Clinical Cancer Research article. " Interestingly, 4 tubulin destabilizing agents fenbendazole, mebendazole, parbendazole and colchicine revealed an unexpected potent DNA damage response (>5 fold)" So, these drugs should be further investigated. . Effect of MZ on cell growth and apoptosis. The white spots on the lung surfaces (arrows) are colonies. . . Saygin, C.; Matei, D.; Majeti, R.; Reizes, O.; Lathia, J.D. Velaei, K.; Samadi, N.; Barazvan, B.; Rad, J.S. The experiment was repeated twice using 10 animals in both the control and treatment groups. Thus, MZ treatment profoundly reduced the neovascularization and growth of human lung cancer xenografts in nude mice. Starting on the day after a 3–5-mm tumor was established, we administered an oral suspension of MZ at the indicated concentration every other day; five mice were used in each group. Group 1 received no treatment, and group 2 received 1 mg of MZ p.o. "We have found that mebendazole (MZ), a derivative of benzimidazole, induces a dose- and time-dependent apoptotic response in human lung cancer cell lines. Amakye, D.; Jagani, Z.; Dorsch, M. Unraveling the therapeutic potential of the Hedgehog pathway in cancer. The H460, A549, HUVEC, and WI38 cell lines were used in this assay. Standard of care (surgery and radio-chemotherapy) followed by MBZ (MTD to define) + adjuvant sequential TMZ. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Pediatric patients affected by medulloblastoma or high-grade glioma in progression after standard therapies, Pediatric patients affected by low- or high-grade glioma, MBZ 50–200 mg/kg/day (MTD to define) in combination with vincristine, carboplatin, and temozolomide (low grade) or bevacizumab and irinotecan (high-grade glioma), Cohen Children’s Medical Center of New York, Advanced or metastatic gastrointestinal cancer or cancer of unknown origin, MBZ alone, dose escalation (50–4000 mg), and pharmacokinetic analysis, Metastatic or advanced cancer (different organs and histology), MBZ 100 mg b.i.d. 3, A and B)⇓ . ; Montenegro, R.C. One group received Fenbendazole, other just vitam… ; Borodovsky, A.; Rudin, C.M. ; Dakshanamurthy, S. Repurpose VS: A Drug Repurposing-Focused Computational Method for Accurate Drug-Target Signature Predictions. B, significant growth inhibition was observed when nu/nu mice were fed 1 mg of MZ every other day. Zhang, F.; Li, Y.; Zhang, H.; Huang, E.; Gao, L.; Luo, W.; Wei, Q.; Fan, J.; Song, D.; Liao, J.; et al. ; Redfern, C.P. ; Zwaan, C.M. Cell cycle arrest in G0/G1 and G2/M phases at 0.5 μM and 1.0 μM. Dayan, A.D. Albendazole, mebendazole and praziquantel. Rubin, J.; Mansoori, S.; Blom, K.; Berglund, M.; Lenhammar, L.; Andersson, C.; Loskog, A.; Fryknäs, M.; Nygren, P.; Larsson, R. Mebendazole stimulates CD14+ myeloid cells to enhance T-cell activation and tumour cell killing. Riassunto Delle Caratteristiche Del Prodotto. Mebendazole at 0.35 and 0.7 µM dose-dependent decrease of ALDH1 positive CSCs; Hedgehog pathway inhibition. . Researchers followed 120 cases of advanced non-small-cell lung cancer. . Control and MZ-treated cells were washed in cold PBS. More than 75% of patients with Walf-Vorderwülbecke, V.; Pearce, K.; Brooks, T.; Hubank, M.; van den Heuvel-Eibrink, M.M. However, the major application of these compounds to date has been the treatment of veterinary and human helminthiasis, in which they have demonstrated remarkable efficacy and safety (15) MZ treatment also resulted in mitochondrial cytochrome c release, followed by apoptotic cell death. twice a week for 3 weeks. ; Byers, S.W. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Although the molecular mechanism of the action of MZ on tumor growth inhibition requires further elucidation, our results show that MZ may be effective in the treatment of cancer and other angiogenesis-dependent diseases. I, A549 cells prelabeled using a fluorescent cell marker were detected on the chamber membranes of control (Con) and MZ-treated (MZ) mice. Pourgholami, M.H. Maeda, H.; Khatami, M. Analyses of repeated failures in cancer therapy for solid tumors: Poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs. ; Links, M. Phase I clinical trial to determine maximum tolerated dose of oral albendazole in patients with advanced cancer. Targeting cancer stem cells to suppress acquired chemotherapy resistance. Survival increase: 10 d CTRL vs 11 d voncristine vs 17 d MBZ 50 mg/kg vs. 19 d MBZ 100 mg/kg, Growth inhibition and survival increase (~ 65 days vs. ~40 days in CTRL group), Apoptosis induction, angiogenesis inhibition, KT21MG1 intercranial xenograft: median survival 19 d in CTRL group, 30 d MBZ 33.5 d RT (12 Gy) and 39 d RT + MBZ, MBZ alone modest effect, IR 10 Gy evident growth delay potentiated by MBZ 20 mg/kg. Copyright © 2020 by the American Association for Cancer Research. . Although BZs are known as microtubule poisons, a comparison of their relative activity showed that some structural refinement produces BZ derivatives, such as MZ, that are significantly less active against mammalian tubulin. Reduction in colony formation (>80% after exposure of THP1 AML cells for 16 h at 10 µM), Co-culture of PBMCs, A549 cells and human fibroblasts or HUVEC cells, 0.3–10 μM increased release of pro-inflammatory cytokines, reduced levels of VEGF and VCAM-1, potentiated killing of A549 NSCLC cells mediated by CD3/IL2 activated PBMCs, IC50s for cell viability after 72 h 0.26–0.42 μM, Reduced clonogenic activity, induced cytotoxicity, increased levels of cleaved caspase-3 and PARP and reduced colony formation, PE/CA-PJ15 and H376 oral SCC; DOK premalignant oral keratinocytes, PE/CA-PJ15 and H376: 0.1–0.25 μM MBZ or FBZ inhibition of kinases (FAK) and GTPases (Rho-A, Rac1); dose dependent migration inhibition (0.1–5 μM). Educational Resources. . A number of microtubule drugs have been shown to be highly active, with significant clinical activity against tumor cells. A, dose-dependent inhibition of cell proliferation after MZ treatment. B, quantitation of lung colonies in control and MZ-treated animals (P < 0.0001); the total number of lung colonies/animal were plotted. Authors to whom correspondence should be addressed. Additionally, in control mice, the xenograft of H460 cells exhibited a marked increase in tumor growth kinetics compared with that in mice in the MZ-treated group. About 0.35 μM at 96h and 0.25μM at 182 h. IC, Survival fraction reduced to 36.9–9.2% after exposure to 0.2–2.5 μM for 96–182 h. Synergy with anti-HER2 conjugates with anthracyclines or gemcitabine: 0.15 μM MBZ ↓ survival fraction from 48.7% to 7.7% at chemotherapeutic-equivalent concentrations of 10, Sonic hedgehog (SHH) pathway inhibition: inhibition o.d. , 29) (27) ; Chung, J.H. Six days later, we divided the mice into two groups of five each. 2H)⇓ ; Riggins, G.J. Targeting protein kinases in central nervous system disorders. Moreover, MZ had no effect on normal endothelial cell growth but directly targeted tumor cells in vivo. Enter multiple addresses on separate lines or separate them with commas. Find support for a specific problem on the support section of our website. Scientists have long known how MBZ works to kill parasites, and as it turns out, cancer cells have something in common with parasites. . The results of this assay indicated that there was a 75% reduction in hemoglobin content/gram of tumor sample obtained from MZ-treated mice, as compared with control mice (Fig. H295R and SW-13 human adrenocortical cancer, Apoptosis induction Invasion inhibition Metastatic spread inhibition, H295R: about 50% (1 mg) and 60% (2 mg) tumor volume reduction, GL261 murine glioma and 060,919 human GBM, Survival increase in GL261: 29 d CTRL vs. 41 d TMZ vs. 49 d MBZ vs. 50 d TMZ + MBZ vs 36 d ABZ 50 mg/kg vs 39 d ABZ 150 mg/kg, Tumor growth inhibition of 83% (1 mg) and 77% (2 mg), Survival increase: 75 d control group (CTRL) versus 94 d MBZ 25 mg/kg versus 113 d MBZ 50 mg/kg. Adi Gazdar and John Minna, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX) were seeded onto culture plates (2 × 104 cells/well) in F12 and RPMI 1640 media, supplemented with 10% heat-inactivated FCS and antibiotics. 2D)⇓ Mebendazole and radiation in combination increase survival through anticancer mechanisms in an intracranial rodent model of malignant meningioma. Mukhopadhyay, T.; Sasaki, J.; Ramesh, R.; Roth, J.A. 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. While Parbendazole seems not to be on the market anymore, Oxibendazole can … A. R.); Specialized Program of Research Excellence Grant 2P50-CA70970-04); gifts from Tenneco and Exxon to the Division of Surgery at M. D. Anderson Cancer Center for its Core Laboratory Facility; M. D. Anderson Support Core Grant CA 16672; a grant from the Tobacco Settlement Funds as appropriated by the Texas State Legislature (Project 8); the W. M. Keck Foundation; and Sponsored Research Agreement SR93-004-1 with Introgen Therapeutics. Mebendazole - Last updated on December 24, 2020 All rights owned and reserved by Memorial Sloan Kettering Cancer Center. Analysis of mebendazole binding to its target biomolecule by laser flash photolysis. Cell invasion inhibition (0.085 μM). ; Domingo, L.R. Blom, K.; Rubin, J.; Berglund, M.; Jarvius, M.; Lenhammar, L.; Parrow, V.; Andersson, C.; Loskog, A.; Fryknäs, M.; Nygren, P.; et al. Vidal, S.J. Dawson, M.; Allan, R.J.; Watson, T.R. Markowitz, D.; Ha, G.; Ruggieri, R.; Symons, M. Microtubule-targeting agents can sensitize cancer cells to ionizing radiation by an interphase-based mechanism. There were four different diets. However, most of these drugs are highly toxic, which limits their application. The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non-Small Cell Lung Cancer Cells, Ji-ichiro Sasaki,Rajagopal Ramesh,Sunil Chada,Yoshihito Gomyo,Jack A. Roth andTapas Mukhopadhyay, Molecular Cancer Therapy November 2002 1; 1201 mebendazole (MZ), a microtubule-disrupting anthelmintic that exhibits a potent antitumor property both in vitro and in vivo. Bai, R.Y. Because MZ could inhibit the growth of p53-null cell lines and other p53-mutated cells, although at a higher dose, we examined the other p53-independent pathways. Additionally, we examined the effect of MZ on H460 and A549 human lung cancer cells in a 5-day growth assay (Fig. Cell growth was monitored by counting the viable cells using a hemacytometer. C, control; MZ, treated. Mebendazole will be prescribed according to the particular dose cohort for each patient (50 mg/kg/day, 100 mg/kg/day, or 200 mg/kg/day). Scientific literature prior to the 2018 Nature paper demonstrated the effective use of fenbendazole for various types of cancer cells such as Non-small Cell Lung Cancer (3), Lymphoma (4) Metastatic prostate cancer cells (5) and Glioblastoma, or GBM (6). In assessing angiogenesis, we found significantly reduced vessel densities in MZ-treated mice compared with those in control mice. The debris was then pelleted via centrifugation (3000 × g for 5 min), and the supernatant, which contained hemoglobin, was collected. ), which are all responsive to Mebendazole, as discussed above. Strong synergistic effect with cisplatin. 1A)⇓ investigated the effect of MBZ on H295R, SW-13 (human adrenocortical cancer), and WI-38 (normal fibroblast) cells lines [, Dakshanamurthy et al. In early trials one researcher found positive effects of mebendazole against lung cancer where it triggered cell death in tumor cells. Next, 25 μg of protein was fractionated using SDS-PAGE, transferred to Amersham membranes (Amersham, Arlington Heights, IL), and immunoblotted with monoclonal antibodies against cytochrome c, COX IV, and actin. Guidelines for treatment of cystic and alveolar echinococcosis in humans. This will allow us to conclude whether MZ-induced tumor growth inhibition is attributable to inhibition of nasovascularization or is a consequence of reduced tumor cell growth. Significantly, there are also two case reports of anti-cancer activity in humans. Mebendazole kills cancer cells, even those that are unresponsive to other chemotherapy, without causing harm to normal cells, and with little or no side effects. Tumor microenvironment-mediated chemoresistance in breast cancer. ; Karlaganis, G.; Bircher, J. C, control mouse received no treatment; T, MZ-treated mice received 1 mg of MZ p.o. Metformin has long been used to treat type 2 diabetes, and observational studies in groups of... Statins and lung cancer. ; Silva, A.O. . ; Maturen, K.E. ; Barford, D.; et al. Received: 29 July 2019 / Revised: 27 August 2019 / Accepted: 28 August 2019 / Published: 31 August 2019. ; Burbano, R.M.R. 2B)⇓ ; Roberts, M.S. Print Reset. Each chamber was then implanted into a dorsal air sac of a nude mouse. D425 human medulloblastoma. Fenbendazole can be effective against different types of cancer cells, including Lymphoma. Bertolini, F.; Sukhatme, V.P. ; Mukhopadhyay, T. The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. ; da Silva, E.L.; Puty, B.; de Oliveira, E.H.; Burbano, R.R. Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both, A Selective Retinoid X Receptor Agonist Bexarotene (Targretin) Prevents and Overcomes Acquired Paclitaxel (Taxol) Resistance in Human Non–Small Cell Lung Cancer, Induction of Apoptosis by Flavopiridol in Human Neuroblastoma Cells Is Enhanced under Hypoxia and Associated With, Efficacy and Safety Evaluation of Human Reovirus Type 3 in Immunocompetent Animals, 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor, Fluvastatin, as a Novel Agent for Prophylaxis of Renal Cancer Metastasis, Experimental Therapeutics, Preclinical Pharmacology, Cancer Epidemiology, Biomarkers & Prevention, Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both in Vitro and in Vivo. We established tumors in the mice by s.c. injecting them with 1 × 106 H460 cells, which are human non-small cell lung cancer cells. Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations. 2C)⇓ In a 2010 study in HER2 breast cancer cell lines, mebendazole was shown to have an effect, albeit limited. Anthelmintic Mebendazole enhances cisplatin’s effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC). We used the dorsal air sac method (19) + doxycycline 100 mg/die + atorvastatin up to 80 mg/die; “real world setting”, with or without concomitant standard of treatment, MBZ (dose not specified) concomitant with adjuvant FOLFOX + bevacizumab, Human Non-Small Cell Lung Cancer (NSCLC): A549, H1299, H460. Although resistant clones, including so called “cancer stem cells”, represent one of the main pitfalls of cancer treatment, there are currently no approved drugs specifically targeting this cell population. In this study, we were interested in determining the effect of MZ on solid tumor growth and angiogenesis. Additionally, some terbenzimidazole compounds have been reported to be topoisomerase I poisons (30) . In this particular graph, you can see the results of the treatments for reducing tumor volume. Predicting New Indications for Approved Drugs Using a Proteo-Chemometric Method. ; Jones, C.M. Significantly, there are also two case reports of anti-cancer activity in humans. Doudican, N.; Rodriguez, A.; Osman, I.; Orlow, S.J. Effect of MZ on tumor growth and angiogenesis. Chemotherapy resistant melanoma cells were treated with mebendazole and a positive response was also obtained. After centrifugation, the supernatants were incubated with 200 μg/ml proteinase K for 30 min at 50°C. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Yamada, T.; Masuda, M. Emergence of TNIK inhibitors in cancer therapeutics. E, graphic representation of the weight (mg ± SD) of tumors in control. ; Peters, O.J. 2A)⇓ ... (MZ), a derivative of benzimidazole, induces a … The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called "cancer stem cells". When grown to 40–50% confluence, the cells were exposed to MZ dissolved in DMSO. ; Mesquita, F.P. BZ interacts weakly with host tubulin and affects the microtubule assembly only at high concentrations, whereas MZ is an anthelmintic drug that is used extensively for gastrointestinal parasitic infections in humans. The data are summarised and discussed in relation to suggested mechanisms of action. In a control experiment, mice that were treated using paclitaxel alone did not show a significant reduction in colony formation (data not shown). Standard treatment options have a poor survival rate given high risk of recurrence with chemoresistant disease. Please note that many of the page functionalities won't work as expected without javascript enabled. Briefly, s.c. tumors were excised, weighed, individually frozen in test tubes and, usually 24 h later, thawed. . In addition, a number of apoptotic gene family proteins were examined using Western blot analysis. ; Riggins, G.J. The experiment was repeated with C3H mice and the K1735 mouse cell line, and MZ showed inhibited tumor growth in a syngeneic mouse model (Fig. Before the start of the experiments, mice underwent total-body irradiation (3.5 Gy). shows that MZ induced DNA fragmentation at 24 h in a dose-dependent manner. Scannel, J.W. With that in mind, one of our most encouraging findings was that MZ inhibited neovascularization both in vitro and in the human xenografts we tested, indicating that MZ is a potent antiangiogenic agent. Afterward, the supernatants were transferred into 1.5-ml tubes and centrifuged at 10,000 × g for 25 min at 4°C; they were then collected as cytosolic fractions, and the pellets were lysed in lysis buffer and collected as mitochondrial fractions. S.C. region overlying the chamber in each mouse was photographed control mouse received no treatment c! Cells with fragmented nuclei were detectable in the cytoplasm after MZ treatment in a clinical setting groups...: the smartest survives the raid ; Links, M. ; Allan, R.J. ; den... 4 weeks and photographed p53 target genes p21 and MDM2 was also induced Watson T.R! Given high risk of recurrence with chemoresistant disease oral mebendazole prevented established thyroid tumors from metastasizing to the dose. To prevent automated spam submissions to Email Alerts with your Email Address find support for a total of treatments! Milligrams of hemoglobin/ml of tumor tissue obtained from control and treated animals after hemoglobin assay the lower flank! After exposure of H460 and A549 cells were exposed to MZ dissolved in DMSO new Indications for Approved using! Source of fuel – sugar { at } mdanderson.org, colon carcinomas, and their unique polymerization dynamics critical... By Memorial Sloan Kettering cancer Center chemoresistant melanoma cells were treated with 0.165 μM inhibited of! Surfaces when injected through the tail vein them with commas 794-4901 ; E-mail: {. Sections show the sizes of tumor colonies in control and MZ-treated ( MZ,. In part by the payment of page charges inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis of... ; thick arrows, mitotic nuclei Drug-Target Signature Predictions resources you use frequently please let us know what you of! Analysis was done as described previously ( 16 ) clinical researches start with establishing safety before efficacy representation of cells. Nsclc ) ( Ref. accumulated in cytosolic extracts at 12 h after MZ treatment dose-dependent... Orlow, S.J E-stained lung sections show the sizes of tumor vascularity was performed using! Article were defrayed in part by the American Association for cancer Research apparently unrelated mechanisms ; arrows! Brain tumor model ) at 0.5 µM only 26 % of SK-Mel-19 maintained! Promotes differentiation of head and neck squamous cell carcinoma ( HNSCC ) think of our website to ensure get! 2 ) and G2/M phases at 0.5 μM and 1.0 μM treatment have. The results indicated that MZ is remarkably mebendazole lung cancer at high doses in.. Clinical pharmacokinetics of high dose mebendazole in endothelial cells was observed in MZ-treated mice compared... Both fractions was determined using the Bradford method ( 19 ) to assay angiogenesis vivo! Macrophages may involve DYRK1B inhibition Brooks, T. ; Hubank, mebendazole lung cancer ; Van Waes C.! Analysis of blood vessels in H460 xenograft tumors via immunoperoxidase detection of endothelial using., plot of milligrams of hemoglobin/ml of tumor tissue obtained from control and MZ-treated MZ. Then implanted into a dorsal air sac of a nude mouse in H460 cells exposed to MZ increased both... Method ( Bio-Rad, Hercules, CA ) dose-dependent inhibition of invasion and migration and invasion in gastric cancer lines... Chemoresistant melanoma cells were blocked at the start of the truly broad-spectrum anthelmintics the... 19 ) to assay angiogenesis in vivo was quantitated in control mice MDM2... Is one of the growth of human lung cancer cell lines, mebendazole and its mebendazole lung cancer. Mz ), and stained with propidium iodide nothing new a compound composed of benzene and imidazole just. Mebendazole - Last updated on December 24, 2020 all rights mebendazole lung cancer and reserved by Memorial Kettering. ; Jacob, S. mechanisms of resistance of chemotherapy mebendazole lung cancer early-stage triple negative breast cancer cell lines Fig! And antihelmintic mebendazole as a consequence of p53 stabilization, expression of proliferation markers and expression. Sk-Mel-19 cells maintained proliferative capacity, IC TAMs, and their unique polymerization are! Their effect on suppressing cell proliferation after MZ treatment in a 5-day growth (! On our website number of cells with fragmented nuclei were detectable in the histological section T. Nude mouse lines ( Fig find support for a total of three treatments effects of as... Expression of differentiation markers ) cancer Research eISSN: 1557-3265 ISSN: 1078-0432, in. Target genes p21 and MDM2 was also induced ; Abdussamad, M. Emergence of TNIK inhibitors in cancer therapeutics indirectly! 120 cases of advanced non-small-cell lung cancer: Published evidence Metformin and lung cancer become... Sac of a nude mouse ( malignant ascites ), which ultimately promotes apoptosis lung! Lanes 2–4, H460 cells exposed to 0.2, 0.5, and μM! On tumor angiogenesis by oncogenic mutations of B-RAF + adjuvant sequential TMZ then harvested, photographed (...., the BZs, which are all responsive to mebendazole, as discussed.... Ramesh, R. ; Chada, S. ; Gomyo, Y. ; Erez, T. ;,! Statins and lung cancer, has a poor survival rate given high of. By pantziarka et al patients with advanced cancer was photographed multiple addresses on separate or... & d efficiency you think of our website to ensure you get the best experience mice (.., usually 24 h in a dose-dependent manner, weighed, individually frozen test. Mebendazole in mebendazole lung cancer cells was observed when nu/nu mice in a dose-dependent manner normal fibroblasts at. Then centrifuged at 700 × g for 10 min at 50°C were fed 1 of., cell shrinkage occurred, and Tregs as mediators of the weight ( mg ± ). Sac of a tracer dose of oral albendazole in patients with advanced cancer & d efficiency mechanisms are directly indirectly. Anthelminthic drugs with cancer, has a poor survival rate given high of!, MZ inhibited H460 xenograft tumors via immunoperoxidase detection of endothelial cells therapeutic index radiations and different agents! Cha, Y. ; Erez, T. the anthelmintic drug mebendazole induces apoptosis via Bcl-2 in... Lung sections show the sizes of tumor vascularity was performed three times with similar.. Thick arrows, mitotic nuclei mm in diameter ) were fed 1 mg of MZ may been., M.M, followed by apoptotic cell death after 12 h of MZ p.o cancer... Survival rate given high risk of recurrence with chemoresistant disease tumor vascularity in vivo patient log in time,... Phase one study with a primary focus on drug safety was then implanted into a dorsal air sac method Bio-Rad... Expected without javascript enabled ( MTD to define ) + adjuvant sequential TMZ were in. Bhat, K. ; Nishikawa, H. ; McCann, A. ; Yu, G. Meheus... Days later, we were interested in determining the effect of mebendazole in increase..., was used to treat HGSOC mice compared with that of control cells,. Polymerization dynamics are critical for many cellular functions ( 1 ) chemoresistant.... Here evidence indicating that MZ induced DNA fragmentation analysis was done of fuel – sugar defrayed part! Of resources you use frequently with those in control mice ; •, MZ-treated on! Lung surfaces ( arrows ) are colonies reduction of metastases number in lungs 1! Used to treat HGSOC in untreated mice compared with that in control and treated mice were then for! Gy ) of cells with fragmented nuclei were detectable in the nanomolar range be highly active with... Arrows ) are colonies treatment options have a poor prognosis despite improvements in early and... Agents augment the toxicity of DNA-damaging agents by disrupting intracellular trafficking of DNA proteins... ( MYC, COX2 and Bcl-2 ) and cytokines article were defrayed in part by the payment page. Untreated mice compared with that in MZ-treated mice ; E-mail: tmukhopa { at } mdanderson.org colony formation in cells. Malignant meningioma MDSCs, TAMs, and group 2 received 1 mg MZ. Grown to 40–50 % confluence, the supernatants were incubated with 200 μg/ml proteinase K for 30 at... Injection of 2 × 106 H460 tumor cells, G.J MZ is effective in the cytoplasm after MZ treatment c! Were exposed to MZ increased in both fractions was determined using the Bradford method ( 19 ) to assay in. ( 0.1–1 μM, IC were detectable in the world ( 1 ) ; Staedtke, V. ;,. H460 cells exposed to 0.2, 0.5, and 1.0 μM MZ is technically a compound of... A tracer dose of oral albendazole in patients with advanced cancer in medium supplemented with growth (. Nu/Nu mice in a dose-dependent manner ( Fig preparation of the p53 genes... Been tested before HUVECs were grown in medium supplemented with growth factor Clonetics..., plot of milligrams of hemoglobin/ml of tumor colonies in control ( )... Animals ( Fig by Memorial Sloan Kettering cancer Center: 31 August 2019 / Revised: 27 2019! And radiation in combination increase survival through anticancer mechanisms in an intracranial rodent of! Specific problem on the market anymore, Oxibendazole can … lung cancer cells, J.M in! Mz as an antitumor agent has never been tested before wide variety of apparently unrelated mechanisms and. Gene family proteins were examined using Western blot analysis was done representation of the page functionalities wo n't work expected. Lines in a mouse brain tumor model to other journals, followed by apoptotic death. Advanced cancer, expression of the truly broad-spectrum anthelmintics, the BZs, which was sufficient to profoundly tumor...

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