Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.
In: Cancer biology & therapy, Jg. 18 (2017-08-03), Heft 8, S. 571-583
Online
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Zugriff:
The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.
Titel: |
Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.
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Autor/in / Beteiligte Person: | Mukhopadhyay, A ; Hanold, LE ; Thayele Purayil, H ; Gisemba, SA ; Senadheera, SN ; Aldrich, JV |
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Zeitschrift: | Cancer biology & therapy, Jg. 18 (2017-08-03), Heft 8, S. 571-583 |
Veröffentlichung: | 2015- : Philadelphia, PA : Taylor & Francis ; <i>Original Publication</i>: Georgetown, TX : Landes Bioscience, c2002-, 2017 |
Medientyp: | academicJournal |
ISSN: | 1555-8576 (electronic) |
DOI: | 10.1080/15384047.2017.1345384 |
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