scholarly journals Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human colorectal cancer cells

2003 ◽  
Vol 374 (2) ◽  
pp. 481-488 ◽  
Author(s):  
Alun HUGHES ◽  
Nicholas I. SMITH ◽  
Heather M. WALLACE

Naproxen, sulindac and salicylate, three NSAIDs (non-steroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N1-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells showed typical signs of apoptosis, and this was confirmed by DNA fragmentation and measurement of caspase-3-like activity. Re-addition of spermidine to the cells partially prevented apoptosis and recovered the cell number. Thus polyamines appear to be an integral part of the signalling pathway mediating NSAID toxicity in human colorectal cancer cells, and may therefore also be important in cancer chemoprevention in humans.

2017 ◽  
Vol 11 (2) ◽  
pp. 90 ◽  
Author(s):  
Jae Hoon Cha ◽  
Woo Kyoung Kim ◽  
Ae Wha Ha ◽  
Myung Hwan Kim ◽  
Moon Jeong Chang

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 499 ◽  
Author(s):  
Misael Corral ◽  
Heather M. Wallace

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.


Sign in / Sign up

Export Citation Format

Share Document