Differential effects of anti-metastatic mechanism of Tian-Xian liquid (TXL) and its bioactive fractions on human colorectal cancer models

J Ethnopharmacol. 2011 Sep 1;137(1):403-13. doi: 10.1016/j.jep.2011.05.035. Epub 2011 Jun 6.

Abstract

Aim of study: This study aimed to elucidate and compare the anti-metastatic mechanism of Tian-Xian liquid (TXL) and its bioactive components namely butanol (BU), ethyl-acetate (EA) and aqueous (WA) fractions on human colorectal cancer in vitro (HT-29 cancer cells) and in vivo (nude mouse xenografts).

Materials and methods: The anti-proliferative effects of TXL and its bioactive components in HT-29 cells were determined by MTT assay. Their modulations on the potential angiogenic and metastatic marker expressions on HT-29 cells and xenografts were investigated by real-time PCR and Western blot at transcriptional and translational levels, respectively. For the in vitro study, migration abilities of HT-29 cells were determined using wound healing assay. For the in vivo study, daily measurements of the tumor size and volume of the xenografts were also performed.

Results: TXL, BU, EA and WA effectively inhibited the proliferation of HT-29 cells in a dose- and time-dependent manner. The IC(50) value of TXL on HT-29 cells was obtained after incubation with 1% (v/v) TXL for 4h; whereas IC(50) values were obtained for the following bioactive components: BU at 1.25% (v/v); EA at 5% (v/v); and WA at 0.3125% (v/v). It was found that 1% (v/v) TXL significantly down-regulated MMP2 and MMP7 expression at both transcriptional and translational levels and it reduced MMP9 and VEGF protein expression in vitro. TXL decreased the metastatic ability of HT-29 cells as demonstrated by wound healing assay. TXL and its bioactive fractions caused no significant changes in the body weight indicating lack of toxicity to the xenografts.

Conclusions: In summary, TXL multi-targeted to down-regulate the metastatic markers in both in vitro and in vivo models. However, the effects of its bioactive fractions were not obvious. This study profoundly elucidated the anti-proliferative mechanism of TXL, which is vital for the development of future anti-cancer regime in Chinese medicinal formulations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blotting, Western
  • Butanols / chemistry
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemical Fractionation
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / secondary
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HT29 Cells
  • Humans
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Solvents / chemistry
  • Time Factors
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Water / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Acetates
  • Antineoplastic Agents, Phytogenic
  • Butanols
  • Drugs, Chinese Herbal
  • Solvents
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • tian-xian
  • Water
  • ethyl acetate
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9