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Updated: Mar 29, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

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

Weixiong Guo1,2, Lanlan Yin2,3, Qiang Wu2

  • 1Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

Antioxidants (Basel, Switzerland)
|March 28, 2026
PubMed

Insights

Carnosic acid (CA) fights osteosarcoma (OS) by stopping cancer cell growth and triggering cell death. It works by activating the STING/IRF3 pathway and boosting nitric oxide, offering a potential new cancer therapy.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer with limited treatment options.
  • Carnosic acid (CA), a natural compound, exhibits anticancer properties, but its mechanism in OS is not well understood.

Purpose of the Study:

  • To investigate the anticancer effects and underlying mechanisms of Carnosic acid (CA) in human osteosarcoma cells.
  • To explore the role of the STING/IRF3 pathway and nitric oxide (NO) in CA-mediated anti-OS activity.

Main Methods:

  • Assessed CA's impact on osteosarcoma cell proliferation and apoptosis in vitro.
  • Investigated the activation of the STING/IRF3 pathway and nitric oxide (NO) production following CA treatment.
  • Utilized pharmacological inhibitors and siRNA to block STING and NO synthesis.
  • Evaluated CA's efficacy in a xenograft mouse model of osteosarcoma.

Main Results:

  • CA significantly suppressed osteosarcoma cell proliferation and induced apoptosis in a dose-dependent manner.
  • CA treatment activated the STING/IRF3 signaling pathway and increased nitric oxide (NO) production.
  • Inhibition of STING or NO synthesis attenuated CA-induced apoptosis in vitro.
  • CA treatment reduced tumor growth in vivo, with partial reversal upon STING inhibition.

Conclusions:

  • Carnosic acid demonstrates significant antitumor effects against osteosarcoma.
  • The mechanism involves the activation of the STING/IRF3 pathway and modulation of nitric oxide production.
  • CA represents a potential therapeutic agent for osteosarcoma, combining antioxidant and immunomodulatory properties.
Keywords:
STING/IRF3 pathwayapoptosiscarnosic acidnitric oxideosteosarcoma

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