Antizyme-dependent and -independent mechanisms are responsible for increased spermidine transport in amino acid-restricted human cancer cells

Amino acid deprivation can inhibit tumour cell proliferation. Since polyami nes are required for cell growth, we hypothesised that their regulatory pat h ways can respond to amino acid restriction. We report here that exposure of human colon adenocarcinoma Caco-2 cells to a medium restricted for a sin gle amino acid, but not for;D-glucose, activates spermidine transport.:The increase was rapid and seemed transient with a maximum 4-6 hr after amino a cid removal. Kinetics showed that the maximal velocity of transport was sol ely increased in L-methionine- or L-leucine-deprived cells, indicating incr eased number of transporters. The intracellular level of complex of ornithi ne decarboxylase (ODC) with antizyme, a negative regulator of polyamine tra nsport, was decreased by 16-29% in amino acid-deprived cells. However, expo sure to limited amounts of amino acid increased transport without altering the ODC-antizyme complex level. We propose that antizyme-independent mechan isms, sensitive to the amino acid concentration, also participate to the co ntrol of spermidine transport. (C) 1999 Academic Press.