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 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.
Myhre
Louise
L
Department of Cell and Organism Biology, Lund University, Sweden.
Alm
Kersti
K
Johansson
Maria
M
Oredsson
Stina M
SM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000187:drug effects / Q000378:metabolism; D056751:Cyclin A2; D019926:Cyclin B / Q000187:drug effects / Q000378:metabolism; D056744:Cyclin B1; D019927:Cyclin E / Q000187:drug effects / Q000378:metabolism; D004247:DNA; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015513:Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C503721:CCNA2 protein, human; C534699:CCNB1 protein, human; C475820:CCNE1 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D015513:Oncogene Proteins; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine; D004247:DNA; D001973:Bromodeoxyuridine