Multivalent Lactulose-amines as Inhibitors of Prostate Cancer Metastasis.

摘要

The purpose of this research is to develop and test a new unique class of potential antimetastatic agents, lactulose-amines (LAs), which may act through targeting human cancer cell adhesion mechanisms and specifically inhibit metastatic cancer cell aggregation, clonogenic growth and induce apoptosis of target cells. In Year 2, we have developed a synthetic approach to the preparation of various multivalent LAs for biochemical and biological studies. As a result of this work, a general synthetic procedure for multivalent LAs have been developed; a total of 2T mono-, bi-, tri-, tetra-, hexa and octavalent LAs have been prepared and characterized. Several of LAs demonstrated high inhibitory potential against clonogenic growth and proliferation of human prostate carcinoma cell lines in vitro. In addition, high affinities to galectin-1, carbohydrate receptor implicated in prostate cancer metastasis, were found for multivalent LAs. Combination of a chosen LA with cancer immunotherapy in a mouse model strongly inhibited tumors in vivo.