Related Experiment Video
Updated: Aug 9, 2025
08:29
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
14.8K
Silibinin, an HSP90 Inhibitor, on Human ACTH-Secreting Adenomas.
Francesca Pecori Giraldi1,2, Maria Francesca Cassarino2, Antonella Sesta2
1Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Neuroendocrinology
|February 15, 2023
Summary
Silibinin, a heat shock protein 90 (HSP90) inhibitor, reduced ACTH secretion in human corticotroph adenomas. This study suggests silibinin as a potential treatment for Cushing's disease by targeting HSP90.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Glucocorticoid receptor (GR) function is crucial for controlling corticotrophin (ACTH) secretion.
- Impaired GR sensitivity characterizes human corticotroph adenomas (Cushing's disease), a condition with limited therapeutic options.
- Silibinin, a heat shock protein 90 (HSP90) inhibitor, has shown potential in tumoral corticotroph cells.
Purpose of the Study:
- To investigate the in vitro effects of silibinin on human corticotroph adenomas.
- To assess silibinin's impact on ACTH secretion and glucocorticoid receptor (NR3C1) gene expression.
Main Methods:
- Seven human ACTH-secreting pituitary adenomas were cultured.
- Treated with varying concentrations of silibinin, with or without dexamethasone, for up to 72 hours.
- Measured ACTH levels and assessed POMC and NR3C1 gene expression.
Main Results:
- Silibinin inhibited spontaneous ACTH secretion and modulated sensitivity to steroid negative feedback in a patient-specific manner.
- POMC expression decreased in silibinin-sensitive adenomas.
- Silibinin reduced constitutive NR3C1 expression and reversed dexamethasone-induced inhibition.
Conclusions:
- Silibinin effectively inhibits ACTH synthesis and secretion in human corticotroph adenomas.
- Silibinin directly influences NR3C1 gene expression.
- These findings support silibinin as a promising therapeutic agent for Cushing's disease by targeting HSP90.
