Normal-like breast cells, but not breast cancer cells, recovered from treatment with N ',N ''-diethylnorspermine

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 G(2) + M phases, followed by a G(1)/S block. The p53/p21/RB1 pathway was involved in the G(1)/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 G(1)/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. Anti-Cancer Drugs 20:230-237 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.