A Novel Membrane-Permeable, Breast-Targeting, Pro-Apoptotic Peptide for Treatment of Breast Cancer
Abstract
In this project, we tried to create a novel peptide with three properties: membrane permeable, breast targeting, and inducing apoptosis. The peptide is expected to be able to induce apoptosis specifically in breast cancer cells and will be tested as a single therapeutic agent as well as in combination with chemotherapeutic drugs to treat breast cancer. For specific aim 1, we have synthesized the breast-targeting, membrane permeable, pro-apoptotic peptide. The BH3 peptide of Bid (EDIIRNIARHLAQVGDSMDR) has been synthesized with eight darginine residues at the N-terminus with a glycine linker residue, followed by a breast-homing sequence (CPGPEGAGC) at the C-terminal. A control peptide with a mutation in the BH3 domain was also synthesized, r8-BH3(L/E)-CPGPEGAGC. Next, we have tested the therapeutic efficacy of the peptide in treatment of breast cancer. The peptide was tested for apoptosis induction first in vitro in cultured breast cancer MCF-7 cells. However, this peptide failed to induce apoptosis in MCF-7 cells at the concentrations being tested. We tried to produce an alternative peptide, which has similar design and predicted functions but with stronger apoptosis inducing capability. The synthesis of the new peptide was not completed. In parallel studies, we have developed a novel strategy using Valproic acid to enhance apoptosis induced by TRAIL in cancer cells. The effects of VPA on apoptosis appear to be due to the down-regulation of survivin and Bcl-XL
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA474733
Entities
People
- Bin Guo
Organizations
- North Dakota State University