Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment

Mol Nutr Food Res. 2024 Jan;68(2):e2300569. doi: 10.1002/mnfr.202300569. Epub 2023 Dec 7.

Abstract

Scope: The optimization of anti-cancer drug effectiveness through dietary modifications has garnered significant attention among researchers in recent times. Astaxanthin (AST) has been identified as a safe and biologically active dietary supplement.

Methods and results: The tumor-bearing mice are treated with sorafenib, along with supplementation of 60 mg kg-1 AST during the treatment. The coadministration of AST and a subclinical dosage of 10 mg kg-1 sorafenib demonstrates a tumor inhibition rate of 76.5%, which is notably superior to the 45% inhibition rate observed with the clinical dosage of 30 mg kg-1 sorafenib (p < 0.05). The administration of AST leads to a tumor inhibition increase of around 25% when combined with the clinical dose of 30 mg kg-1 sorafenib (p <0.05). AST enhances the inhibitory effect of sorafenib on tumor angiogenesis through the JAK2/STAT3 signaling pathway. Furthermore, AST exhibits a reduction in hypoxia within the tumor microenvironment.

Conclusion: The results suggest that AST supplement enhances the inhibitory effects of sorafenib on hepatocellular carcinoma. This study presents a new dietary management program for oncology patients.

Keywords: astaxanthin; dietary supplementation; hepatocellular carcinoma; sensitizing effect; sorafenib.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Humans
  • Hypoxia / drug therapy
  • Janus Kinase 2 / metabolism
  • Janus Kinase 2 / pharmacology
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Mice
  • Niacinamide / pharmacology
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use
  • STAT3 Transcription Factor*
  • Signal Transduction
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use
  • Tumor Microenvironment
  • Xanthophylls

Substances

  • Sorafenib
  • astaxanthine
  • Phenylurea Compounds
  • Antineoplastic Agents
  • Niacinamide
  • JAK2 protein, human
  • Janus Kinase 2
  • STAT3 protein, human
  • Xanthophylls
  • STAT3 Transcription Factor