Celastrus orbiculatus extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo

Chin J Integr Med. 2012 Oct;18(10):752-60. doi: 10.1007/s11655-011-0819-7. Epub 2011 Jul 30.

Abstract

Objective: Celastrus orbiculatus Thunb. has been used for thousands of years in China as a remedy against cancer and inflammatory diseases. This study aims to investigate whether C. orbiculatus extract (COE) could inhibit angiogenesis, which is the pivotal step in tumor growth, invasiveness, and metastasis.

Methods: In this study, the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10, 20, 40, 80, and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any antiangiogenic effects.

Results: COE significantly inhibited proliferation and induced apoptosis in Hepa1-6 cells and inhibited VEGF expression at both mRNA and protein levels. Furthermore, this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo, COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis.

Conclusions: In summary, COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Celastrus / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Drug Combinations
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Laminin / metabolism
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Physiologic / drug effects
  • Phytotherapy
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Stems / chemistry
  • Proteoglycans / metabolism
  • Signal Transduction* / drug effects
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Drug Combinations
  • Laminin
  • Plant Extracts
  • Proteoglycans
  • Vascular Endothelial Growth Factor A
  • matrigel
  • Collagen