Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice

J Pharmacol Sci. 2016 Oct;132(2):131-137. doi: 10.1016/j.jphs.2016.09.003. Epub 2016 Sep 14.

Abstract

The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA) in the treatment of hepatocellular carcinoma (HCC). RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β) were measured by enzyme linked immunosorbent assays (ELISA). Protein levels of phosphorylated NF-κB p65 and p65 were detected by western blot. mRNA level of NF-κB p65 was analyzed by qRT-PCR. The results showed that RA could effectively suppress tumor growth with fewer toxic effects by regulating the secretion of cytokines associated with inflammation and angiogenesis, and suppressing the expression of NF-κB p65 in the xenograft microenvironment. Our findings unveil the possible anti-tumor mechanisms of RA and support RA as a potential drug for the treatment of HCC.

Keywords: Angiogenesis; Hepatocellular carcinoma; Inflammation; NF-κB p65; Rosmarinic acid.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Depsides / pharmacology
  • Depsides / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Male
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cinnamates
  • Depsides
  • Inflammation Mediators
  • NF-kappa B
  • rosmarinic acid