# The Modulation of Cell Plasticity by Budesonide: Beyond the Metabolic and Anti-Inflammatory Actions of Glucocorticoids

## TL;DR

Budesonide, a drug used for inflammation, also affects stem and cancer cell behavior and prevents viral infections, beyond its known anti-inflammatory effects.

## Contribution

Budesonide modulates cell plasticity and inhibits cancer cell motility, revealing new therapeutic potential beyond its anti-inflammatory role.

## Key findings

- Budesonide stabilizes cell–cell adhesions and prevents embryonic stem cell differentiation.
- It inhibits the motility of breast, lung, and pancreatic cancer cells.
- Budesonide prevents infection by RNA viruses like SARS-CoV-2.

## Abstract

The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, and colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression of pro-inflammatory cytokines/chemokines and the recruitment of immune cells into the inflamed mucosa. However, emerging evidence indicates that BUD, unlike classical glucocorticoids, is also a potent modulator of stem and cancer cell behavior/plasticity. Certainly, BUD stabilizes cell–cell adhesions, preventing embryonic stem cell differentiation and inhibiting the development of 3D gastruloids. In addition, BUD inhibits the motile/invasive propensity of different cancer cells, including breast, lung, and pancreatic cancer. Finally, it prevents the infection of positive single-stranded human-infecting RNA viruses such as SARS-CoV-2. At a molecular level, BUD induces epigenetic changes and modifies the transcriptome of epithelial, stem, and cancer cells, providing molecular support to the immune cell-independent activity of BUD. Here, we performed an in-depth review of these unexpected activities of BUD, identified by unbiased drug screening programs, and we emphasize the molecular mechanisms modulated by this efficacious drug that deserve further research.