1. Regulation of p21, MMP-1, and MDR-1 expression in human colon carcinoma HT29 cells by Tian Xian liquid, a chinese medicinal formula, in vitro and in vivo.
- Author
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Sze SC, Wong KL, Liu WK, Ng TB, Wong JH, Cheung HP, Yow CM, Chu ES, Qing Liu, Hu YM, Tsang KW, Lee WS, and Yao Tong
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Animals, CDC2 Protein Kinase biosynthesis, CDC2 Protein Kinase genetics, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Colonic Neoplasms genetics, Colonic Neoplasms pathology, Cyclin-Dependent Kinase Inhibitor p21 genetics, Drugs, Chinese Herbal adverse effects, Drugs, Chinese Herbal chemistry, Gene Expression Regulation, Neoplastic drug effects, HT29 Cells, Humans, Matrix Metalloproteinase 1 genetics, Mice, Mice, Nude, Proliferating Cell Nuclear Antigen biosynthesis, Proliferating Cell Nuclear Antigen genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, Drugs, Chinese Herbal pharmacology, Matrix Metalloproteinase 1 biosynthesis
- Abstract
Ethnopharmacological Relevance: Tian-Xian liquid (TXL), a commercially available Chinese medicine decoction, has been used as an anticancer dietary agent for more than 10 years without reported side effects., Aim of the Study: The safety and quality consistency of TXL and its mechanisms of action on antiproliferation, antimetastasis, and reversion of multidrug resistance (MDR) regimens were explored., Materials and Methods: In this study, an atomic absorption spectrophotometer and reversed phase high performance liquid chromatography with photodiode array detection (HPLC-DAD) were used to evaluate the main toxic elements and the quality consistency among different batches of TXL extracts, respectively. HT29 human colon cancer cell line and tumor-bearing nude mice were used. TXL was provided by China-Japan Feida Union Company Limited. The effect of TXL on in vitro proliferation of HT29 human colon cancer cell line was examined. The percentages of treated cells distributed in different phases of the cell cycles were analyzed by flow cytometry. Antiproliferative effect after treatment with TXL was assessed by determination of the protein levels of p21, cyclinD1, PCNA, and cdk-2, which are the key regulators for cell cycle progression. Meanwhile, the protein levels of MMP-1 and MDR-1 (multidrug resistance protein-1) were also determined to assess the effect of TXL on antimetastasis and reversion of MDR regimen, respectively., Results: The contents of main toxic elements were lower in TXL extract compared with the standard set by the Department of Health of the Government of Hong Kong Special Administrative Region (SAR). Our HPLC results showed that the relative standard deviations of the amount of the 5 standards were less than 5% in different batches of TXL. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of cyclinD1, PCNA, and cdk-2 in the TXL-treated in vitro models, thereby, impeding cell progression from G1/S phase. Results obtained from the in vivo study also demonstrated that TXL upregulated the protein level of p21 and downregulated the protein levels of MMP-1 and MDR-1., Conclusions: Results obtained from the present investigation not only demonstrate the safety and quality of TXL extract but also demonstrate that TXL possesses antiproliferative and antimetastatic activities and brings about reversion of MDR on HT29 cell and on xenografted tissue in tumor-implanted nude mice., (© The Author(s) 2011)
- Published
- 2011
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