2. Academic Validation
  3. Carnosic Acid Activates the STING/IRF3 Pathway to Induce Nitric Oxide-Mediated Apoptosis in Osteosarcoma Cells

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

  • Antioxidants (Basel). 2026 Mar 16;15(3):374. doi: 10.3390/antiox15030374.
Weixiong Guo 1 2,  Lanlan Yin 2 3,  Qiang Wu 2,  Jiaqi Chu 1 2 4
Affiliations

Affiliations

  • 1 Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
  • 2 The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China.
  • 3 Reproductive Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
  • 4 Stem Cell Research and Cellular Therapy Center, Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
PMID: 41897520 DOI: 10.3390/antiox15030374
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.

Keywords

STING/IRF3 pathway; apoptosis; carnosic acid; nitric oxide; osteosarcoma.

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