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Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of Pituitary Adenoma Cells by Hampering Oncogenic Pathways and Promoting Apoptotic Signaling
| Content Provider | MDPI |
|---|---|
| Author | Justo, Castaño Gesmundo, Iacopo Granato, Giuseppina Fuentes-Fayos, Antonio Alvarez, Clara Dieguez, Carlos Zatelli, Maria Congiusta, Noemi Banfi, Dana Prencipe, Nunzia Leone, Sheila Brunetti, Luigi Luque, Raúl Cai, Renzhi Sha, Wei Ghigo, Ezio Schally, Andrew Granata, Riccarda |
| Copyright Year | 2021 |
| Description | Pituitary adenomas (PAs) are intracranial tumors, often associated with excessive hormonal secretion and severe comorbidities. Some patients are resistant to medical therapies; therefore, novel treatment options are needed. Antagonists of growth hormone-releasing hormone (GHRH) exert potent anticancer effects, and early GHRH antagonists were found to inhibit GHRH-induced secretion of pituitary GH in vitro and in vivo. However, the antitumor role of GHRH antagonists in PAs is largely unknown. Here, we show that the GHRH antagonists of MIAMI class, MIA-602 and MIA-690, inhibited cell viability and growth and promoted apoptosis in GH/prolactin-secreting GH3 PA cells transfected with human GHRH receptor (GH3-GHRHR), and in adrenocorticotropic hormone ACTH-secreting AtT20 PA cells. GHRH antagonists also reduced the expression of proteins involved in tumorigenesis and cancer progression, upregulated proapoptotic molecules, and lowered GHRH receptor levels. The combination of MIA-690 with temozolomide synergistically blunted the viability of GH3-GHRHR and AtT20 cells. Moreover, MIA-690 reduced both basal and GHRH-induced secretion of GH and intracellular cAMP levels. Finally, GHRH antagonists inhibited cell viability in human primary GH- and ACTH-PA cell cultures. Overall, our results suggest that GHRH antagonists, either alone or in combination with pharmacological treatments, may be considered for further development as therapy for PAs. |
| Starting Page | 3950 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13163950 |
| Journal | Cancers |
| Issue Number | 16 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-08-05 |
| Access Restriction | Open |
| Subject Keyword | Cancers Endocrinology and Metabolism Ghrh Gh-secreting Pituitary Adenoma Acth-secreting Pituitary Adenomas Cell Viability Apoptosis |
| Content Type | Text |
| Resource Type | Article |
