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

E.S.M. Chu, S.C.W. Sze, H.P. Cheung, K.L. Wong, Q. Liu, T.B. Ng, Y. Tong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 IC50 value of TXL on HT-29 cells was obtained after incubation with 1% (v/v) TXL for 4 h; whereas IC50 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.

Graphical abstract
Schematic figure demonstrated the anti-metastatic effect of a traditional Chinese medicinal decoction, Tian-Xian liquid (TXL), on human colorectal cancer in vitro and in vivo.
Original languageEnglish
Pages (from-to)403-413
Number of pages11
JournalJournal of Ethnopharmacology
Volume137
Issue number1
Early online date6 Jun 2011
DOIs
Publication statusPublished - 1 Sep 2011
Externally publishedYes

Scopus Subject Areas

  • Medicine(all)

User-Defined Keywords

  • Chinese medicinal formulation
  • Tian-Xian liquid
  • Matrix metalloproteinases
  • Vascular endothelial growth factor
  • Anti-metastatic
  • Colorectal cancer

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