Cytoplasmic alkalinization induced by activation of the Na+ H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+ H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 μm) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 μm after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 μM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.
|Number of pages||5|
|State||Published - Dec 1992|
Bibliographical noteFunding Information:
Correspondence: Courtney M. Townsend, Jr, MD, Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555, USA. *Visiting scientist from The Department of Internal Medicine, Kosin Medical College, Pusan, Korea. tvisiting surgeon from the University of Witwatersrand, Johannesburg, South Africa, supported by scholarship from the Michael and Janie Miller Foundation and Medical Research Council, South Africa. This work was supported by grants from the American Cancer Society (PDT-220) and the National Institutes of Health (NIH) PO1 DK 35608, 5R37 DK 15241).
- colon cancer
- ornithine decarboxylase
ASJC Scopus subject areas