Amiloride inhibits the growth of human colon cancer cells in vitro.
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 microM) 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 microM 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 microM) 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.
Koo
J Y
JY
Department of Surgery, University of Texas Medical Branch, Galveston 77555.
Parekh
D
D
Townsend
C M
CM
Saydjari
R
R
Evers
B M
BM
Farre
A
A
Ishizuka
J
J
Thompson
J C
JC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D000584:Amiloride / Q000627:therapeutic use*; D000704:Analysis of Variance; D015317:Biogenic Polyamines / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D015317:Biogenic Polyamines; D000584:Amiloride; D009955:Ornithine Decarboxylase