Membrane disrupting lytic peptide conjugates destroy hormone dependent and independent XXXX cells in vitro and in vivo.

@entity1 @entity4396 @entity137 @entity263 @entity0 @entity535 @entity19 @entity53 @entity230
We have prepared conjugates of a membrane disrupting lytic peptide (hecate) and a 15- @entity535 segment of the beta-chain of CG and hecate and the decapeptide, @entity4396 ( @entity4396 ). We have tested the concept that these conjugates will target @entity0 cells expressing LH/CG or @entity4396 receptors. In previous studies, we were able to destroy @entity263 in vitro and in vivo with lytic peptide conjugates. Hecate, hecate-betaCG and @entity4396 -hecate were added to cultures of the @entity1 @entity0 cell lines MCF-7 and MDA-MB-435S. Hecate and its conjugates showed concentration dependent @entity137 to both cell lines. The lytic peptide alone showed similar EC50 values for both cell lines; however, there was a significant difference between the EC50 values when the conjugates were tested. The hormone dependent MCF-7 cell line was less sensitive to the betaCG conjugate than to the @entity4396 conjugate; the reverse was found for the hormone independent @entity1 cells. Removal of @entity230 decreased the sensitivity of MCF-7 cells to both lytic peptide conjugates and this sensitivity could be restored by adding @entity53 . Activation of protein kinase C further increased the sensitivity to the drug. MDA-MB-435S xenografts were established in intact female athymic @entity19 , which were treated once a week for 3 weeks with hecate-betaCG via the lateral tail vein. The ability of hecate-betaCG to destroy xenografts of @entity1 @entity0 cells (MDA-MB-435S) in @entity19 was demonstrated for the first time. We conclude that hecate-betaCG and @entity4396 -hecate conjugates could serve as useful drugs for the treatment of @entity0 .
