Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Metformin, an AMPK Activator and mTOR Inhibitor, Suppresses Cancer Stem Cells
2.2. Metformin Suppresses Key Enzymes of the Mevalonate Pathway
2.3. Metformin Reduced CSCs through Inhibition of Protein Prenylation, rather than Cholesterol Synthesis, in the MVA Pathway
2.4. Tumor-Suppressing Effect of Metformin in a Murine Xenograft Model Was Reversed by Additional Treatment with Mevalonate
3. Discussion
4. Methods
4.1. Cell Lines and Culture Conditions
4.2. Tumor Sphere Culture Assay
4.3. Microarray Data Analysis Using a Public Data Set
4.4. Flow-Cytometric Analysis and Fluorescence-Activated Cell Sorting (FACS)
4.5. RNA Extraction and qPCR
4.6. Western Blotting
4.7. Drugs and Antibodies
4.8. In Vivo Mouse Xenograft Experiments
4.9. Immunohistochemistry
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Seo, Y.; Kim, J.; Park, S.J.; Park, J.J.; Cheon, J.H.; Kim, W.H.; Kim, T.I. Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer. Cancers 2020, 12, 2554. https://doi.org/10.3390/cancers12092554
Seo Y, Kim J, Park SJ, Park JJ, Cheon JH, Kim WH, Kim TI. Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer. Cancers. 2020; 12(9):2554. https://doi.org/10.3390/cancers12092554
Chicago/Turabian StyleSeo, Yoojeong, Janghyun Kim, Soo Jung Park, Jae Jun Park, Jae Hee Cheon, Won Ho Kim, and Tae Il Kim. 2020. "Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer" Cancers 12, no. 9: 2554. https://doi.org/10.3390/cancers12092554