Mebendazole is an antiparasitic which can bind nematode tubulin and cause inhibition of intestinal microtubule synthesis. It also inhibits Hh signaling, targeting SMO. Mebendazole was sufficient to reduce ShhN-induced expression of endogenous GLI1 and PTCH1 to basal levels at 0.1μM in the immortalized human retinal pigment epithelial cell line hTERT-RPE1. Similarly, there was partial reduction in GLI1 and PTCH1 transcripts at 0.1μM mebendazole and almost complete suppression at 1μM mebendazole, on the human medulloblastoma cell line DAOY. This inhibition of Hh signaling by Mebendazole led decrease of cell proliferation and survival, and increase apoptosis. Daily gavage of Mebendazole at dose of 50mg/kg for 38 days extended the median survival of DAOY orthotopic tumor xenograft mice. Mebendazole at 1μM decreased activation of SMO shown by the Gli-luc and Renilla reporter in NIH3T3 fibroblasts maintained in low-serum conditions for 48 hours. Mebendazole suppressed the formation of the primary cilium, a microtubule based organelle that functions as a signaling hub for Hh pathway activation. Combination of vismodegib and mebendazole resulted in additive Hh signaling inhibition[5].
Mebendazole/甲苯咪唑 细胞实验
Cell Line
Concentration
Treated Time
Description
References
UW228 medulloblastoma cells
1 μM
24 hours
To evaluate the effect of MBZ on tubulin polymerization in UW228 cells. Results showed 1 μM MBZ significantly reduced tubulin polymerization in UW228 cells.
Neuro Oncol. 2015 Apr;17(4):545-54.
D425 medulloblastoma cells
1 μM
24 hours
To evaluate the effect of MBZ on tubulin polymerization in D425 cells. Results showed 1 μM MBZ had no significant effect on tubulin polymerization in D425 cells.
Neuro Oncol. 2015 Apr;17(4):545-54.
Human umbilical vein endothelial cells (HUVECs)
1-10 μM
30 minutes
To investigate the inhibition of MBZ on VEGFR2-Y1175 autophosphorylation. Results showed MBZ significantly inhibited VEGFR2-Y1175 autophosphorylation at 1-10 μM.
Neuro Oncol. 2015 Apr;17(4):545-54.
060919 human GBM neurosphere cells
0.1 μM
72 hours
Evaluate the cytotoxicity of mebendazole on 060919 cells, showing an IC50 of approximately 0.1 μM.
Neuro Oncol. 2011 Sep;13(9):974-82.
GL261 mouse glioma cells
0.24 μM
72 hours
Evaluate the cytotoxicity of mebendazole on GL261 cells, showing an IC50 of 0.24 μM.
Neuro Oncol. 2011 Sep;13(9):974-82.
FPD-MM cells
1000 nM
24 hours
MB treatment reduced chromatin accessibility and protein expression
Blood Cancer J. 2024 Feb 5;14(1):25.
GMR-AML1 cells
>300 nM
72 hours
MB treatment induced loss of viability in GMR-AML1 cells
Blood Cancer J. 2024 Feb 5;14(1):25.
HL1 cardiomyocytes
6.25 μM
Mebendazole increased cardiomyocyte viability
Sci Transl Med. 2014 Dec 10;6(266):266ra170.
MDA-MB-468
0.5 μM
24 hours
To evaluate the inhibitory effect of Flubendazole on TNBC cell proliferation, results showed that Flubendazole significantly inhibited cell proliferation
Theranostics. 2020 Jul 2;10(18):8080-8097.
MDA-MB-231
0.5 μM
24 hours
To evaluate the inhibitory effect of Flubendazole on TNBC cell proliferation, results showed that Flubendazole significantly inhibited cell proliferation
Theranostics. 2020 Jul 2;10(18):8080-8097.
Mebendazole/甲苯咪唑 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
GMR-AML1-Luc/GFP xenograft model
20 mg/kg and 40 mg/kg
3 weeks and 4 weeks
MB monotherapy significantly reduced leukemia burden and improved survival
Blood Cancer J. 2024 Feb 5;14(1):25.
Zebrafish
Doxorubicin-induced cardiomyopathy model
1 μM
48 hours
Mebendazole protected zebrafish from doxorubicin-induced cardiotoxicity and death
Sci Transl Med. 2014 Dec 10;6(266):266ra170.
Nude mice
PTCH1-mutant medulloblastoma allograft model and D425 medulloblastoma xenograft model
Oral gavage
50 mg/kg
Once daily, continuous treatment
To evaluate the effect of MBZ on survival and tumor angiogenesis in medulloblastoma models. Results showed MBZ significantly extended survival in PTCH1-mutant and D425 medulloblastoma models and inhibited tumor angiogenesis.
Neuro Oncol. 2015 Apr;17(4):545-54.
C57BL/6 mice
GL261 syngeneic glioma model
Oral gavage
50 mg/kg
Daily for the first 20 days, then 5 days per week
Evaluate the therapeutic effect of mebendazole on the GL261 glioma model, showing mean survival extended from 30 days to 49 days, a 63.3% increase.
Neuro Oncol. 2011 Sep;13(9):974-82.
Nude mice
Xenograft tumor model
Subcutaneous injection
20 mg/kg
Once daily until the end of the experiment
To evaluate the anti-tumor effect of Flubendazole in vivo, results showed that Flubendazole significantly inhibited tumor growth
Theranostics. 2020 Jul 2;10(18):8080-8097.
Immunocompromised mice
PDX-0003 (p53 null) and PDX-0030 (p53 positive)
Oral gavage
10 mg/kg, 25 mg/kg and 50 mg/kg
Three times per week for three weeks
To evaluate the therapeutic effect of fenbendazole on ovarian cancer PDX models, results showed that all doses of fenbendazole significantly inhibited tumor growth.
Recurrent B Acute Lymphoblasti... 展开 >>c Leukemia
Refractory B Acute Lymphoblastic Leukemia 收起 <<
Phase 1
Recruiting
November 2020
United States, Pennsylvania
... 展开 >>
Sidney Kimmel Cancer Center at Thomas Jefferson University
Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Margaret Kasner, MD 215-955-8874 margaret.kasner@jefferson.edu
Principal Investigator: Margaret Kasner, MD 收起 <<
Recurrent B Acute Lymphoblasti... 展开 >>c Leukemia
Refractory B Acute Lymphoblastic Leukemia 收起 <<
Phase 1
Recruiting
November 2020
United States, Pennsylvania
... 展开 >>
Sidney Kimmel Cancer Center at Thomas Jefferson University
Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Margaret Kasner, MD 215-955-8874 margaret.kasner@jefferson.edu
Principal Investigator: Margaret Kasner, MD 收起 <<
United States, South Carolina
... 展开 >>
Addiction Sciences Division-Medical University of South Carolina
Recruiting
Charleston, South Carolina, United States, 29425
Contact: Megan M Moran-Santa Maria, Ph.D. moranm@musc.edu
Contact: Francis M Beylotte, MS 8437922522 ext Beylotte beylott@musc.edu
Sub-Investigator: Julianne Flanagan, Ph.D.
Principal Investigator: Sudie Back, Ph.D. 收起 <<
United States, Maryland
... 展开 >>
Atavistic Chemotherapy Clinical Trial
Bethesda, Maryland, United States, 20814
Mexico
Dr. Frank Arguello Cancer Clinic
San Jose del Cabo, Baja California Sur, Mexico
Instituto de Ciencia y Medicina Genomica
Torreon, Coahuila, Mexico 收起 <<
United States, California
... 展开 >>
Childrens Hospital Los Angeles
Recruiting
Los Angeles, California, United States, 90027
Contact: Girish Dhall 323-361-4629 gdhall@chla.usc.edu
Principal Investigator: Girish Dhall
Lucile Packard Children Hospital Stanford University
Recruiting
Palo Alto, California, United States, 94304
Contact: Paul G. Fisher 650-721-5889 pfisher@stanford.edu
Principal Investigator: Paul G. Fisher
United States, District of Columbia
Childrens National Medical Center
Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Eugene Hwang, MD 202-476-5046 ehwang@childrensnational.org
Principal Investigator: Lindsay B Kilburn, MD
Sub-Investigator: Roger Packer, MD
Sub-Investigator: Brain Rood, MD
Sub-Investigator: Eugene Hwang, MD
United States, Illinois
Lurie Childrens Hospital-Chicago
Recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman 312-227-4874 sgoldman@luriechildrens.org
Principal Investigator: Stewart Goldman, MD
Sub-Investigator: Jason Fangusaro, MD
Sub-Investigator: Rishi Lulla, MD
Sub-Investigator: Natasha Pillay-Smiley, MD
United States, New York
Memorial Sloan Kettering Cancer Center
Recruiting
New York, New York, United States, 10065
Contact: Ira Dunkel 212-639-2153 dunkeli@mskcc.org
Principal Investigator: Ira Dunkel
United States, North Carolina
Duke University Medical Center
Recruiting
Durham, North Carolina, United States, 27710
Contact: David Van Mater, MD, PhD 919-684-3401 david.vanmater@duke.edu
Principal Investigator: David Van Mater
United States, Ohio
Cincinnati Children Hospital Medical Center
Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Maryam Fouladi 513-803-0721 maryam.fouladi@cchmc.org
Principal Investigator: Maryam Fouladi
United States, Pennsylvania
Children Hospital of Pittsburgh of UPMC
Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Ian Pollack 412-692-5881 Pollaci@chp.edu
Sub-Investigator: Ian Pollack, MD
Principal Investigator: A. Kim Ritchey, MD
United States, Tennessee
St. Jude Children Research Hospital
Recruiting
Memphis, Tennessee, United States, 38105
Contact: Giles Robinson, MD 901-595-2907 giles.robinson@stjude.org
Principal Investigator: Zsila Sadighi, MD
Sub-Investigator: Amar Gajjar, MD
United States, Texas
Texas Childrens Hospital
Recruiting
Houston, Texas, United States, 77030
Contact: Patricia M. Baxter, MD 832-824-4681 pabaxter@txch.org
Sub-Investigator: Murali M. Chintagumpala
Principal Investigator: Patricia Baxter
United States, Washington
Seattle Children Hospital
Recruiting
Seattle, Washington, United States, 98105
Contact: Sarah Leary 206-987-2106 sarah.leary@seattlechildrens.org
Principal Investigator: Sarah Leary 收起 <<
Benin
... 展开 >> Institut de Recherche pour le Développement
Recruiting
Comé, Benin
Contact: Adrian Luty, PhD, DR adrian.luty@ird.fr
India
Christian Medical College
Recruiting
Vellore, India
Contact: Gagandeep Kang, MBBS, MD, PhD gkang@cmcvellore.ac.in
Malawi
London School of Hygiene and Tropical Medicine
Recruiting
Mangochi, Malawi
Contact: Robin Bailey, MA, BM, MRCP, DTM&H, PhD, FRCP robin.bailey@lshtm.ac.uk 收起 <<
United States, California
... 展开 >>
Stanford University, School of Medicine
Recruiting
Palo Alto, California, United States, 94304
Contact: Hari Priya M. Yerraballa 650-724-9363 yhpriya@stanford.edu
Principal Investigator: Sanjiv Gambhir 收起 <<
United Kingdom
... 展开 >> The Atherstone Surgery
Not yet recruiting
Atherstone, United Kingdom, CV9 1EU
Contact: Jeanette Melrose, MD
University Hospitals Bristol NHS Foundation Trust- Location Bristol Royal Infirmary
Not yet recruiting
Bristol, United Kingdom, IG95LP
Contact: Debbie Shipley, MD
Kings Medical Centre
Buckhurst Hill, United Kingdom, IG95LP
Sheepcot Medical Centre
Not yet recruiting
Watford, United Kingdom, WD25 7NL
Contact: Alan Jackson, MD 收起 <<
Argentina
... 展开 >> Fundacion Huesped
Buenos Aires, Argentina
Australia
Commonwealth Scientific and Industrial Research Organisation
Brisbane, Australia
Queensland Institute for Medical Research, University of Queensland
Herston QLD, Australia
Brazil
Fundação Oswaldo Cruz
Belo Horizonte, Brazil
Cambodia
Institut Pasteur in Cambodia, Clinical Pathology Unit
Phnom Penh, Cambodia
Cameroon
University of Yaoundé I
Yaoundé I, Cameroon
Ethiopia
College of Public Health and Medical Sciences, Jimma University
Jimma, Ethiopia
Tanzania
Ivo de Carneri, Pemba Island
Zanzibar, Tanzania
Vietnam
National Institute for Malariology, Parasitology and Entomology
Hanoi, Vietnam 收起 <<
United States, New York
... 展开 >>
Cohen Children's Medical Center of New York
Recruiting
New Hyde Park, New York, United States, 11040
Contact: Mark P Atlas, MD 718-470-3460 matlas@nshs.edu
Contact: Derek R Hanson, MD 551-996-5437 DHanson@hackensackumc.org
Principal Investigator: Mark P Atlas, MD
Sub-Investigator: Derek R Hanson, MD
Sub-Investigator: Arlene Redner, MD
Sub-Investigator: Mohamad Badawi, MD
Sub-Investigator: Avery Wright, DO 收起 <<
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