Jansma, K.M. (Kirsten Marije) (2014) Targeting Wnt signaling pathway in colorectal cancer stem cells. thesis, Medicine.
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Abstract
Colorectal cancer (CRC) is one of the most lethal types of cancer in the Western world. Even though more effective screening methods and early detection of polyps have led to a decrease in mortality rate, the patient’s prognosis still is poor in general. Recent studies identified the role of cancer stem cells (CSC) in tumor initiation, growth and maintenance of colorectal cancer. These CSC’s are less sensitive to classic cytostatic agents, therefore new targeted therapeutic approaches have to be identified. Stem cell maintenance, cell proliferation, differentiation and apoptosis is partly driven by canonical Wnt/β-catenin signaling pathway, thereby playing an important role in gene transcription. Using phytochemical agents, we tried to inhibit this Wnt/β-catenin signaling pathway in colorectal cancer stem cells. The MTT assay and iCelligence realtime system were used to determine cytotoxicity of these agents. We found strong reduction in cell number in HCT116 cells by all Cucurbitacins, but iCelligence was not appropriate to measure cytotoxicity in CSC’s. By using a β-catenin activation kit, we saw that nuclear β-translocation was reduced after treatment with Cucurbitacin B and Demethoxycurcumin. Apoptosis, measured by Hoechst staining, was induced by Cucurbitacin B, E and Demethoxycurcumin. A significant reduction of LGR5 protein expression was seen in samples treated with Cucurbitacin B, E and Demethoxycurcumin. Our results suggest inhibition of Wnt signaling pathway by Cucurbitacin B and Demethoxycurcumin. Further research is required to determine the potential role of these agents in colorectal cancer therapy.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Jong, Prof. Dr. S. de |
| Supervisor name: | Cheah, Prof. Dr. S.C. and Faculty of Medicine & Health Sciences and UCSI University and Kuala Lumpur, Malaysia |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:50 |
| Last Modified: | 25 Jun 2020 10:50 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1129 |
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