Article: 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

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TitleRegulation 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
AuthorsSze, SCW1
Wong, KL1
Liu, WK3
Ng, TB3
Wong, JH3
Cheung, HP1
Yow, CML2
Chu, ESM1
Liu, Q1
Hu, YM1
Tsang, KW1
Lee, WS1
Tong, Y1
KeywordsChinese medicine decoction
colon cancer
metastasis and multidrug resistance
proliferation
Tian-Xian liquid
Issue Date2011
PublisherSage Publications, Inc.. The Journal's web site is located at http://www.sagepub.com/journalsProdDesc.nav?prodId=Journal201510
CitationIntegrative Cancer Therapies, 2011, v. 10 n. 1, p. 58-69 [How to Cite?]
DOI: http://dx.doi.org/10.1177/1534735410378743
AbstractEthnopharmacological 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.
ISSN1534-7354
2011 Impact Factor: 2.136
2011 SCImago Journal Rankings: 0.157
DOIhttp://dx.doi.org/10.1177/1534735410378743
ISI Accession Number IDWOS:000289157000006
Funding AgencyGrant Number
Seed Funding Programme for Applied Research200807160015
Small Project Funding200807176239
University of Hong Kong
China-Japan Feida Union Company Limited
Funding Information:

This research was supported in part by a grant from Seed Funding Programme for Applied Research (no. 200807160015), Small Project Funding (no. 200807176239), the University of Hong Kong, and the contract research funding from China-Japan Feida Union Company Limited.

ReferencesReferences in Scopus
GrantsMechanical Study of Tian Xian Liquid (TXL), Chinese Medicine Formula, in Treatment of Colon Cancer in vitro
Bioactive components of Tian Xian Liquid as a potential drug candidate for the treatment of colon cancer
DC Field
Value
dc.contributor.authorSze, SCW
dc.contributor.authorWong, KL
dc.contributor.authorLiu, WK
dc.contributor.authorNg, TB
dc.contributor.authorWong, JH
dc.contributor.authorCheung, HP
dc.contributor.authorYow, CML
dc.contributor.authorChu, ESM
dc.contributor.authorLiu, Q
dc.contributor.authorHu, YM
dc.contributor.authorTsang, KW
dc.contributor.authorLee, WS
dc.contributor.authorTong, Y
dc.date.accessioned2010-10-31T13:35:23Z
dc.date.available2010-10-31T13:35:23Z
dc.date.issued2011
dc.description.abstractEthnopharmacological 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.
dc.description.grantMechanical Study of Tian Xian Liquid (TXL), Chinese Medicine Formula, in Treatment of Colon Cancer in vitro
dc.description.grantBioactive components of Tian Xian Liquid as a potential drug candidate for the treatment of colon cancer
dc.description.grantcode99283
dc.description.grantcode99392
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationIntegrative Cancer Therapies, 2011, v. 10 n. 1, p. 58-69 [How to Cite?]
DOI: http://dx.doi.org/10.1177/1534735410378743
dc.identifier.doihttp://dx.doi.org/10.1177/1534735410378743
dc.identifier.epage69
dc.identifier.hkuros197172
dc.identifier.isiWOS:000289157000006
Funding AgencyGrant Number
Seed Funding Programme for Applied Research200807160015
Small Project Funding200807176239
University of Hong Kong
China-Japan Feida Union Company Limited
Funding Information:

This research was supported in part by a grant from Seed Funding Programme for Applied Research (no. 200807160015), Small Project Funding (no. 200807176239), the University of Hong Kong, and the contract research funding from China-Japan Feida Union Company Limited.

dc.identifier.issn1534-7354
2011 Impact Factor: 2.136
2011 SCImago Journal Rankings: 0.157
dc.identifier.issue1
dc.identifier.openurl
dc.identifier.pmid20702488
dc.identifier.scopuseid_2-s2.0-79953704228
dc.identifier.spage58
dc.identifier.urihttp://hdl.handle.net/10722/127608
dc.identifier.volume10
dc.languageeng
dc.publisherSage Publications, Inc.. The Journal's web site is located at http://www.sagepub.com/journalsProdDesc.nav?prodId=Journal201510
dc.publisher.placeUnited States
dc.relation.ispartofIntegrative Cancer Therapies
dc.relation.referencesReferences in Scopus
dc.rightsIntegrative Cancer Therapies. Copyright © Sage Publications, Inc..
dc.subject.meshColonic Neoplasms - drug therapy - genetics - metabolism - pathology
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21 - biosynthesis - genetics
dc.subject.meshDrugs, Chinese Herbal - adverse effects - chemistry - pharmacology
dc.subject.meshMatrix Metalloproteinase 1 - biosynthesis - genetics
dc.subject.meshP-Glycoprotein - biosynthesis - genetics
dc.subjectChinese medicine decoction
dc.subjectcolon cancer
dc.subjectmetastasis and multidrug resistance
dc.subjectproliferation
dc.subjectTian-Xian liquid
dc.titleRegulation 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
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hong Kong Polytechnic University
  3. Chinese University of Hong Kong