Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

Abstract

Abstract : Naure polyamines play an important role in cell proliferation and differentiation. Synthetic polyamine analogues can mimic natural polyamines in the down-regulation of polyamine biosynthesis, but analogues cannot promote cell growth. Our previous results show that polyamine analogues also down-regulate estrogen receptor (ER ), the principle target in human breast cancer therapy. This proposal was designed to investigate the molecular mechanisms and the therapeutic efficacy of oligomines in the treatment of human breast cancer. In the fourth year of this award, we investigated the possible roles of the polyamines biosynthetic pathway in polyamine analogues mediated repress on ER . In our latest studies, we demonstrated that ER expression was repressed after ornithine decarboxylase (ODC), the polyamines biosynthetic key enzyme, was downregulated by siRNA in several human breast cancer cell lines. Apoptosis and cell cycle arrest were also induced. These results indicated that the polyamine synthetic pathway is a key mediator of polyamine analogue induced ER alpha suppression.