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Research Article

In vivo evaluation of mebendazole and Ran GTPase inhibition in breast cancer model system

    Balqis Abu-Hdaib

    Pharmacological & Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan

    ,
    Hamdi Nsairat

    *Author for correspondence: 

    E-mail Address: h.alnseirat@ammanu.edu.jo

    Pharmacological & Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan

    ,
    Mohamed El-Tanani

    **Author for correspondence:

    E-mail Address: eltanani@rakmhsu.ac.ae

    Pharmacological & Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan

    College of Pharmacy, Ras Al Khaimah Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates

    ,
    Ibrahim Al-Deeb

    Pharmacological & Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan

    &
    Nabil Hasasna

    Department of Cell Therapy & Applied Genomics, King Hussein Cancer Center (KHCC), P.O. Box: 1269, Amman, 11941, Jordan

    Published Online:https://doi.org/10.2217/nnm-2023-0351

    Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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