Abstract
Polyamines are essential growth factors that have a positive role in cancer cell growth. Their metabolic pathway and the diverse enzymes involved have been studied in depth in multiple organisms and cells. Polyamine transport also contributes to the intracellular polyamine content but this is less well-studied in mammalian cells. As the polyamine transporters could provide a means of selective drug delivery to cancer cells, a greater understanding of polyamine transport and its regulation is needed. In this study, transport of polyamines and polyamine content was measured and the effect of modulating each was determined in human colorectal cancer cells. The results provide evidence that upregulation of polyamine transport depends on polyamine depletion and on the rate of cell growth. Polyamine transport occurred in all colorectal cancer cell lines tested but to varying extents. The cell lines with the lowest basal uptake showed the greatest increase in response to polyamine depletion. Kinetic parameters for putrescine and spermidine suggest the existence of two separate transporters. Transport was shown to be a saturable but non-polarised process that can be regulated both positively and negatively. Using the polyamine transporter to deliver anticancer drugs more selectively is now a reality, and the ability to manipulate the polyamine transport process increases the possibility of using these transporters therapeutically.
| Original language | English |
|---|---|
| Article number | 499 |
| Number of pages | 10 |
| Journal | Biomolecules |
| Volume | 10 |
| Issue number | 4 |
| Early online date | 25 Mar 2020 |
| DOIs | |
| Publication status | Published - Apr 2020 |
Bibliographical note
Funding: M.C. was funded by CONACyT, Mexico with the PhD scholarship 237771/411030. Acknowledgments: We would like to thank Mark Burns of Aminex Therapeutics for kindly providing theAMXT compounds and P.M. Woster from Medical University of South Carolina for DFMO and Gary Cameron for LC-MS analyes
Author Contributions: M.C. and H.M.W. designed the study. M.C. performed the experiments, interpreted the data and wrote the manuscript. H.M.W. interpreted the data and revised the manuscript. Conceptualisation, Heather M Wallace; funding acquisition, Heather M Wallace; investigation, Misael Corral; methodology, Misael Corral and Heather M Wallace; resources, H.M.W.; supervision, H.M.W.; validation, M.C.; visualisation, M.C.;
writing—original draft, M.C.; writing—review and editing, H.M.W.. All authors have read and agreed to the published version of the manuscript.
Keywords
- polyamines
- putrescine
- spermidine
- uptake
- DFMO
- transport
- drug delivery
- colorectal cancer
- Colorectal cancer
- Drug delivery
- Putrescine
- Polyamines
- Uptake
- Spermidine
- Transport
Access to Document
- Corral_etal_biomolecules_Upregulation_of_polyamine_VOR
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