Low-dose deoxycholic acid stimulates putrescine uptake in colon cancer cells (Caco-2).
Deoxycholic acid (DCA) has long been implicated as tumour-promoting agent in the colon. Polyamines are necessary for cell proliferation, they are accumulated in high amounts in colon cancer cells, and their concentrations in the colonic lumen can reach millimolar levels. The aim of this study was to investigate the effects of physiological DCA concentrations on proliferation and polyamine content in human colon cancer cells (Caco-2) in culture. Over an initial 48 h in culture, DCA stimulated Caco-2 cell proliferation rate three-fold, reaching a maximum with 20 microM DCA. DCA-induced increases in ornithine decarboxylase (ODC) activity corresponded to peak proliferation rates, occurring only during the initial 48 h of cell proliferation. Treatment with low-dose DCA resulted in a two-fold increase in putrescine uptake, first noted after 2 days in culture, but persisting until the cells became confluent (day 5). Both basal and DCA-stimulated putrescine uptake in Caco-2 cells were saturable. Kinetic analysis of the uptake data showed that DCA-stimulated putrescine uptake was due to an increase in the capacity of the putative putrescine transporter, without changes in its affinity, therefore implying an increased number of putrescine transporters in the cell membrane, without change in their structure.
Milovic
V
V
Gastroenterology Unit, Division of Medicine, 4th Floor, North Wing, UMDS/Guy's, King's & St Thomas' Hospitals, Lambeth Palace Road, London, UK. milovic@em-uni-frankfurt.de
Stein
J
J
Odera
G
G
Gilani
S
S
Murphy
G M
GM
D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D011073:Polyamines; D003840:Deoxycholic Acid; D009955:Ornithine Decarboxylase; D011700:Putrescine