# Carnosic Acid Activates the STING/IRF3 Pathway to Induce Nitric Oxide-Mediated Apoptosis in Osteosarcoma Cells

## TL;DR

Carnosic acid fights osteosarcoma by triggering a pathway that boosts nitric oxide and causes cancer cell death.

## Contribution

This study reveals that carnosic acid activates the STING/IRF3 pathway to induce apoptosis in osteosarcoma cells.

## Key findings

- Carnosic acid suppressed osteosarcoma cell proliferation and induced apoptosis dose-dependently.
- CA activates the STING/IRF3 pathway and increases nitric oxide production.
- CA's antitumor effects were partially reversed by STING inhibition in a mouse model.

## Abstract

Osteosarcoma (OS) is a highly aggressive bone cancer with limited therapeutic options. Carnosic acid (CA), a phenolic diterpene with well-established antioxidant properties, has shown anticancer activity, yet its mechanisms in OS remain unclear. In this study, we found that CA suppressed proliferation and induced apoptosis in human osteosarcoma cells in a dose-dependent manner. Mechanistically, CA activated the STING/IRF3 signaling pathway and enhanced nitric oxide (NO) production, factors closely linked to redox modulation and mitochondrial apoptotic signaling. Pharmacological inhibition or siRNA-mediated knockdown of STING, as well as blockade of NO synthesis, significantly reduced CA-induced apoptosis in vitro. In a xenograft mouse model, CA treatment suppressed tumor growth, and this effect was partially reversed by STING inhibition. These findings suggest that CA exerts antitumor effects in OS through modulation of innate immune and redox-related signaling pathways, supporting its potential as a therapeutic compound that links antioxidant and immunomodulatory actions.