Membrane Disrupting Lytic Peptide Conjugates Destroy Hormone Dependent and Independent Breast Cancer Cells in vitro and in vivo
| Autor: | Barbara Gawronska, William Hansel, Carola Leuschner, Frederick M. Enright |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
medicine.medical_specialty Neoplasms Hormone-Dependent Mice Nude Peptide Biology Gonadotropin-Releasing Hormone Mice In vivo Internal medicine Tumor Cells Cultured medicine Animals Chorionic Gonadotropin beta Subunit Human Amino Acid Sequence Receptor chemistry.chemical_classification Cell Membrane luteinizing hormone/choriogonadotropin receptor Mammary Neoplasms Experimental Melitten Xenograft Model Antitumor Assays In vitro Endocrinology Oncology chemistry Cell culture Models Animal Cancer cell Cancer research Female Luteinizing hormone Signal Transduction |
| Zdroj: | Breast Cancer Research and Treatment. 78:17-27 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | We have prepared conjugates of a membrane disrupting lytic peptide (hecate) and a 15-amino acid segment of the beta-chain of CG and hecate and the decapeptide, luteinizing hormone releasing hormone (LHRH). We have tested the concept that these conjugates will target breast cancer cells expressing LH/CG or LHRH receptors. In previous studies, we were able to destroy prostate cancers in vitro and in vivo with lytic peptide conjugates. Hecate, hecate-betaCG and LHRH-hecate were added to cultures of the human breast cancer cell lines MCF-7 and MDA-MB-435S. Hecate and its conjugates showed concentration dependent toxicity 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 LHRH conjugate; the reverse was found for the hormone independent MDA-MB-435S cells. Removal of steroids decreased the sensitivity of MCF-7 cells to both lytic peptide conjugates and this sensitivity could be restored by adding estradiol. Activation of protein kinase C further increased the sensitivity to the drug. MDA-MB-435S xenografts were established in intact female athymic nude mice, 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 human breast cancer cells (MDA-MB-435S) in nude mice was demonstrated for the first time. We conclude that hecate-betaCG and LHRH-hecate conjugates could serve as useful drugs for the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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