Blocking Internalization of Phosphatidylethanolamine at Cleavage Furrow of Mitosis as a Novel Mechanism of Anti-Breast-Cancer Strategy

摘要

During the formation of cleavage furrow of mitosis, phosphatidylethanolamine (PE) flips from inner leaflet of the plasma membrane to the outer leaflet specifically in the furrow region near the contractile ring. Immediately after the contractile ring separates the two daughter cells, PE returns from outer leaflet to inner leaflet. This transient movement of PE during cytokinesis is essential because blockage of this PE movement results in a failure of mitosis and leads to cell death. Cinnamycin produced by Streptoverticillium griseoverticillatum targets specifically to PE on cell surface at the cleavage furrow of mitotic cells but not the non-dividing cells. This proposal is to test if cinnamycin is a better anti-tumor drug for treatment of breast cancers because of several advantages: (1) Cinnamycin only targets proliferating cells but has no effect on non-proliferating cells. (2) The anti- proliferation activity doesn't require cinnamycin to enter the cells. (3) Cinnamycin doesn't have to suffer the effect of multi-drug resistance mechanism or cellular metabolism. Because cinnamycin is no longer available commercially, we had to devise production procedures and to purify this compound in our own lab. Thus, completion of this proposal would require longer time than that was originally proposed.