Publication

The Effect of Mebendazole and RAN Mediated Pathways on Human Breast Cancer Cells

Shahid, Muhammad A.
Publication Date
End of Embargo
Supervisor
Kantamneni, Sriharsha
isreb, mohammad
El-Tanani, Mohamed
Morgan, Richard
Keywords
Breast cancer, Mebendazole, RAN, RCC1, SKIL, GLS, METTL7A, PPP1R15A, Ran inhibition, shRNA Transfection, Ran mediated pathways
Rights
Creative Commons License
The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy and Medical Sciences. Faculty of Life Sciences
Awarded
2023
Embargo end date
Collections
Theses
Show all metadata
Files
PhD Thesis
Adobe PDF, 6.99 MB
Additional title
Abstract
Breast cancer is a prevalent form of cancer that affects millions of people worldwide, accounting for 25% of all female cancers and the second leading cause of cancer-related deaths in women, following lung cancer. Breast cancer metastasis to other body parts is expected, with bones, liver, lungs, and brain as the most frequent sites. Ran, a protein highly expressed in cancer cells, facilitates cell invasion, metastasis, and drug resistance. This study investigated the hypothesis that Mebendazole has anti-cancer activity via Ran and has antiangiogenic effects, which can be repurposed as a therapeutic for breast cancer treatment. Furthermore, the project aims to establish the efficacy of Mebendazole in combination with the known chemotherapy drug Paclitaxel, Doxorubicin, to reduce its dosage concentration and associated side effects and cost of treatment. This study found that Mebendazole reduces cell migration and invasion of breast cancer cells via Ran inhibition. New proteins were identified by determining the Mebendazole effect on the mRNA expression of a panel of 54 genes. This study further analysed the knockdown effect of RAN, RCC1, SKIL, and METTL7A invasion and metastasis of breast cancer cells. Mebendazole also reduced the IC50 of Paclitaxel and downregulated Ran expression in MCF10A, MDA MB231, and MCF7 breast cell lines. Finally, in vivo, a chorioallantoic membrane assay (CAM) was conducted to establish the antiangiogenic effect of Mebendazole. This study presents significant steps toward the clinical validation of Mebendazole as a combination therapy for reducing the invasion and metastasis of breast cancer cells.
URI
https://bradscholars.brad.ac.uk/handle/10454/20270
Version
Citation
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Thesis
Qualification name
PhD
Notes