Aqueous Extract of Bambusae Caulis in Taeniam Inhibits PMA-induced Tumor Cell Invasion and Pulmonary Metastasis: Suppression of NF-κB Activation Through ROS Signaling

PLoS One. 2013 Oct 28;8(10):e78061. doi: 10.1371/journal.pone.0078061. eCollection 2013.

Abstract

Bamboo shavings (Bambusae Caulis in Taeniam, BCT) are widely used as a traditional Chinese medicine to control hypertension and cardiovascular disease, and to alleviate fever, vomiting, and diarrhea. It has been demonstrated that BCT reduces ovalbumin-induced airway inflammation by regulating pro-inflammatory cytokines, and decreases tumor growth in tumor-bearing mice. However, the effects of BCT on the metastatic potential of malignant cancer cells and the detailed mechanism of its anti-metastatic activity have not been examined previously. In this study, we investigated whether an aqueous extract of BCT (AE-BCT) reduces the metastatic potential of HT1080 cells, and elucidated the underlying anti-metastatic mechanism. In addition, we examined whether AE-BCT administration inhibits pulmonary metastasis of intravenously injected B16F10 cells in C57BL/6J mice. AE-BCT (50-250 µg/ml) dose-dependently suppressed colony-forming activity under anchorage-dependent and -independent growth conditions. Pretreatment with AE-BCT efficiently inhibited cell migration, invasion, and adhesion. AE-BCT also dramatically suppressed PMA-induced MMP-9 activity and expression by blocking NF-κB activation and ERK phosphorylation. Production of intracellular ROS, a key regulator of NF-κB-induced MMP-9 activity, was almost completely blocked by pretreatment with AE-BCT. Furthermore, daily oral administration of AE-BCT at doses of 50 and 100 mg/kg efficiently inhibited lung metastasis of B16F10 cells injected into the tail veins of C57BL/6J mice with no systemic toxicity. These results demonstrate that AE-BCT significantly reduced the metastatic activity of highly malignant cancer cells by suppressing MMP-9 activity via inhibition of ROS-mediated NF-κB activation. These results indicate that AE-BCT may be a safe natural product for treatment of metastatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Bambusa / chemistry*
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / analogs & derivatives*
  • Tetradecanoylphorbol Acetate / toxicity

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • NF-kappa B
  • Plant Extracts
  • phorbolol myristate acetate
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate

Grant support

This work has been supported by the a Grant K12050 awarded to Korea Institute of Oriental Medicine (KIOM) from Ministry of Education, Science and Technology (MEST), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.