| Title | Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Au CMC, Furness JB, Britt K, Oshchepkova S, Ladumor H, Soo KYing, Callaghan B, Gerard C, Inghirami G, Mittal V, Wang Y, Huang XYun, Spector JA, Andreopoulou E, Zumbo P, Betel D, Dow L, Brown KA |
| Journal | Elife |
| Volume | 9 |
| Date Published | 2020 07 15 |
| ISSN | 2050-084X |
| Keywords | Acylation, Animals, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Cell Culture Techniques, Cell Line, Tumor, Female, Ghrelin, Humans, MCF-7 Cells, Mice, Mice, Inbred BALB C, Mice, Nude, Mice, SCID, Peptide Fragments, Peptides, Cyclic, Spheroids, Cellular, Xenograft Model Antitumor Assays |
| Abstract | Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531. We report potent anti-tumor effects of unacylated ghrelin, dependent on cells being cultured in 3D in a biologically-relevant extracellular matrix. The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of Gαi and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer. |
| DOI | 10.7554/eLife.56913 |
| Alternate Journal | Elife |
| PubMed ID | 32667883 |
| PubMed Central ID | PMC7363447 |
| Grant List | T32 CA062948 / CA / NCI NIH HHS / United States NC-14-011 / / National Breast Cancer Foundation / International ECF-16-004 / / National Breast Cancer Foundation / International GNT1007714 / / National Health and Medical Research Council / International |
Related Faculty:
Giorgio Inghirami, M.D.