Upregulation of Polyamine Transport in Human Colorectal Cancer Cells
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 w...
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/4/499 |
| _version_ | 1818450953153544192 |
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| author | Misael Corral Heather M. Wallace |
| author_facet | Misael Corral Heather M. Wallace |
| author_sort | Misael Corral |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T20:59:29Z |
| format | Article |
| id | doaj.art-163262b87bf74456b9c6bd287f80866f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-14T20:59:29Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-163262b87bf74456b9c6bd287f80866f2022-12-21T22:47:37ZengMDPI AGBiomolecules2218-273X2020-03-0110449910.3390/biom10040499biom10040499Upregulation of Polyamine Transport in Human Colorectal Cancer CellsMisael Corral0Heather M. Wallace1School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UKSchool of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UKPolyamines 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.https://www.mdpi.com/2218-273X/10/4/499polyaminesputrescinespermidineuptakedfmotransportdrug deliverycolorectal cancer |
| spellingShingle | Misael Corral Heather M. Wallace Upregulation of Polyamine Transport in Human Colorectal Cancer Cells Biomolecules polyamines putrescine spermidine uptake dfmo transport drug delivery colorectal cancer |
| title | Upregulation of Polyamine Transport in Human Colorectal Cancer Cells |
| title_full | Upregulation of Polyamine Transport in Human Colorectal Cancer Cells |
| title_fullStr | Upregulation of Polyamine Transport in Human Colorectal Cancer Cells |
| title_full_unstemmed | Upregulation of Polyamine Transport in Human Colorectal Cancer Cells |
| title_short | Upregulation of Polyamine Transport in Human Colorectal Cancer Cells |
| title_sort | upregulation of polyamine transport in human colorectal cancer cells |
| topic | polyamines putrescine spermidine uptake dfmo transport drug delivery colorectal cancer |
| url | https://www.mdpi.com/2218-273X/10/4/499 |
| work_keys_str_mv | AT misaelcorral upregulationofpolyaminetransportinhumancolorectalcancercells AT heathermwallace upregulationofpolyaminetransportinhumancolorectalcancercells |