A number of
polyamine analogs are currently used in various clinical trials as
cancer treatment and it is important to investigate their effects not only on
cancer cells but also on normal cells. Treatment with
polyamine analogs depletes cells of
polyamines and inhibits cell proliferation, but the analogs cannot take over the normal function of the natural
polyamines in the cell. In this study, the normal-like breast epithelial cell line MCF-10A was treated with the
polyamine analog N',N"-diethylnorspermine (
DENSPM). The cells were then studied using a
bromodeoxyuridine-
DNA flow cytometry method as well as western blot. The ability of both normal-like and
breast cancer cells to recover from
DENSPM treatment was also studied.
DENSPM treatment of MCF-10A cells resulted in a prolongation of the S and G2 +M phases, followed by a G1/S block. The p53/p21/RB1 pathway was involved in the G1/S block as shown by increased levels of p53 and p21 detected by western blot. Decreased levels of
cyclin E1,
cyclin A2, and
cyclin B1 in
DENSPM-treated cells can explain the prolongation of cell cycle phases that occurred before the G1/S block. We also show that MCF-10A cells rapidly recover from
DENSPM-induced growth inhibition in contrast to four human
breast cancer cell lines. The goal of
cancer treatment is to cause minimal and reversible damage to normal cells, while
cancer cells should be eliminated. Altogether, the data show that treatment with
polyamine analogs spares normal cells, while negatively affecting the
cancer cells.