Polyamine Analogues as Novel Anti-HER Family Agents in Human Breast Cancer

Abstract

Abstract : Elevated levels of all three naturally occurring polyamines, spermine, spermidine and putrescine, have been found in breast cancer tissues. Polyamine analogues have been shown to inhibit cell growth and in some cases induce apoptosis. My studies have demonstrated the ability of Progen (PG)-11144 and other oligoamines to inhibit cell growth in human breast cancer cell lines. These oligoamines can also suppress epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and estrogen receptor(ER)-alpha protein in multiple human breast cancer cell lines. Low dose long term exposure of T47D cells to PG-11144 decreases heat shock protein (HSP) 90 in addition to several HER family member proteins while not decreasing other receptors such as vitamin D receptor (VDR) and retinoic acid receptor (RAR)-beta. In addition to T47D cells, RAR-beta protein levels were maintained in MCF7 cells treated with PG-11144. Oligoamines PG-11144 and PG-11150 inhibit the growth of MCF7 and T47D breast cancer cell lines in a time and dose dependent manner. This project demonstrates that polyamine analogues are novel anti-HER family agents and contributes to their cytotoxicity in human breast cancer cells.