The Effect of the Ac-PHSdCN-NH2 Peptide on Prostate Cancer Invasion and Metastasis
Rosendahl, Leslie A.
Prostate cancer, the cause of death for more than 32,000 males in the U.S. each year, is difficult to treat due to the heterogeneity of the disease. Present treatment consists of with hormonal manipulation, which sends the patient into temporary remission followed by the onset of an androgen-independent cancer which may lead to death within 4 to 8 months. The peptide sequence Ac-PHSCN-NH2 has been tested to develop and alternate treatment. In both an in vivo model and an in vitro model the peptide was demonstrated to be effective at blocking invasion and metastasis of MAT-Ly-Lu cells by 40- to greater than 100-fold. To make the peptide even more effective, the cysteine residue was substituted with the D-isomer. This substitution makes the portion of the peptide containing the cysteine residue endoprotease resistant. We hypothesized that, because it is endoprotease resistant, the D-isomer, Ac-PHSdCN-NH2, would be a more effective agent than the L-isomer, Ac-PHSCN-NH2. In this thesis, we tested this hypothesis via experimentation using the in vitro and in vivo models. Our results showed that the D-isomer was equally effective as it reduced metastasis by 30- to more than 100-fold in rats. Additionally we tested the affect of these peptides on a human prostate cancer cell line, DU-145, through experimentation with the in vitro model. In this model the D-isomer was shown to be 100 times more effective at blocking invasion of the DU-145 cells. Thus, while Ac-PHSdCNNH2 was equally effective at treating prostate cancer in rats as Ac-PHSCN-NH2, it may be a more potent and anti-metastatic agent for post-surgical treatment prior to extensive metastasis in humans.
iv, 27 p.
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