Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December 2013 Volume 8 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December 2013 Volume 8 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression

  • Authors:
    • Li Sun
    • Weigang Chen
    • Lili Qu
    • Jie Wu
    • Jin Si
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China, Department of Laboratory Medicine, Hospital of Jianye District, Nanjing, Jiangsu 210000, P.R. China
  • Pages: 1883-1887
    |
    Published online on: October 18, 2013
       https://doi.org/10.3892/mmr.2013.1742
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Multidrug resistance (MDR) of tumor cells is a serious obstacle encountered in cancer treatment. In the current study a multiple drug‑resistant HepG2/adriamycin (HepG2/ADR) cell line was established and its MDR was characterized. Icaritin, an active ingredient isolated from the medical plant Herba Epimedium, was observed to reverse MDR in the present model. Icaritin significantly increased the intracellular accumulation of ADR and decreased the expression of the MDR1 gene in HepG2/ADR cells compared with drug‑sensitive HepG2 cells. In addition, the present results showed that icaritin may significantly downregulate the expression of P‑glycoprotein. These results indicate that icaritin is a novel and potent MDR reversal agent and may be a promising drug for tumor chemotherapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

McKillop IH, Moran DM, Jin X and Koniaris LG: Molecular pathogenesis of hepatocellular carcinoma. J Surg Res. 136:125–135. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar

3 

Trevisani F, Cantarini MC, Wands JR and Bernardi M: Recent advances in the natural history of hepatocellular carcinoma. Carcinogenesis. 29:1299–1305. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Kusakabe A, Tanaka Y, Orito E, Sugauchi F, Kurbanov F, Sakamoto T, Shinkai N, Hirashima N, Hasegawa I, Ohno T, et al: A weak associatioon between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan. J Gastroenterol. 42:298–305. 2007. View Article : Google Scholar : PubMed/NCBI

5 

El-Serag HB, Siegel AB, Davila JA, Shaib YH, Cayton-Woody M, McBride R and McGlynn KA: Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: a population-based study. J Hepatol. 44:158–166. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Wakamatsu T, Nakahashi Y, Hachimine D, Seki T and Okazaki K: The combination of glycyrrhizin and lamivudine can reverse the cisplatin resistance in hepatocellular carcinoma cells through inhibition of multidrug resistance-associated proteins. Int J Oncol. 31:1465–1472. 2007.

7 

Pérez-Tomás R: Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr Med Chem. 13:1859–1876. 2006.PubMed/NCBI

8 

Clarke R, Currier S, Kaplan O, Lovelace E, Boulay V, Gottesman MM and Dickson RB: Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human breast cancer cells. J Natl Cancer Inst. 84:1506–1512. 1992. View Article : Google Scholar : PubMed/NCBI

9 

Choi C: ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int. 5:302005. View Article : Google Scholar : PubMed/NCBI

10 

Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM and Deeley RG: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 258:1650–1654. 1992. View Article : Google Scholar : PubMed/NCBI

11 

Cox DS, Scott KR, Gao H, Raje S and Eddington ND: Influence of multidrug resistance (MDR) proteins at the blood-brain barrier on the transport and brain distribution of enaminone anticonvulsants. J Pharm Sci. 90:1540–1552. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Coley HM: Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer. Cancer Treat Rev. 34:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Xiang W, Gao A, Liang H, Li C, Gao J, Wang Q, Shuang B, Zhang J, Yan Y and Wang X: Reversal of P-glycoprotein-mediated multidrug resistance in vitro by milbemycin compounds in adriamycin-resistant human breast carcinoma (MCF-7/adr) cells. Toxicol in Vitro. 24:1474–1481. 2010. View Article : Google Scholar

14 

Xu HB, Xu LZ, Li L, Fu J and Mao XP: Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines. Eur J Pharmacol. 694:39–44. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M and Brinkmann U: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA. 97:3473–3478. 2000. View Article : Google Scholar

16 

Gottesman MM and Ling V: The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett. 580:998–1009. 2006.PubMed/NCBI

17 

Li J, Xu LZ, He KL, Guo WJ, Zheng YH, Xia P and Chen Y: Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line. Breast Cancer Res. 3:253–263. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Middleton E Jr, Kandaswami C and Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 52:673–751. 2000.PubMed/NCBI

19 

Li YL, Gan GP, Zhang HZ, Wu HZ, Li CL, Huang YP, Liu YW and Liu JW: A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines. J Ethnopharmacol. 113:115–124. 2007.

20 

Diaz JG, Carmona AJ, Torres F, Quintana J, Estévez F and Herz W: Cytotoxic activities of flavonoid glycoside acetates from Consolida oliveriana. Planta Med. 74:171–174. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Wesołowska O: Interaction of phenothiazines, stilbenes and flavonoids with multidrug resistance-associated transporters, P-glycoprotein and MRP1. Acta Biochim Pol. 58:433–448. 2011.PubMed/NCBI

22 

Wang Z, Wang H, Wu J, Zhu D, Zhang X, Ou L, Yu Y and Lou Y: Enhanced co-expression of beta-tubulin III and choline acetyltransferase in neurons from mouse embryonic stem cells promoted by icaritin in an estrogen receptor-independent manner. Chem Biol Interact. 179:375–385. 2009. View Article : Google Scholar

23 

Wo YB, Zhu DY, Hu Y, Wang ZQ, Liu J and Lou YJ: Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells. J Cell Biochem. 103:1536–1550. 2008. View Article : Google Scholar

24 

Zhang G, Qin L, Sheng H, Wang XL, Wang YX, Yeung DK, Griffith JF, Yao XS, Xie XH, Li ZR, Lee KM and Leung KS: A novel semisynthesized small molecule icaritin reduces incidence of steroid-associated osteonecrosis with inhibition of both thrombosis and lipid-deposition in a dose-dependent manner. Bone. 44:345–356. 2009. View Article : Google Scholar

25 

Wang ZQ and Lou YJ: Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells. Eur J Pharmacol. 504:147–153. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Huang X, Zhu D and Lou Y: A novel anticancer agent, icaritin, induced cell growth inhibition, Gl arrest and mitochondrial transmenbrane potential drop in human prostate carcinoma PC-3 cells. Eur J Pharmacol. 564:26–36. 2007. View Article : Google Scholar

27 

Hall MD, Brimacombe KR, Varonka MS, Pluchino KM, Monda JK, Li J, Walsh MJ, Boxer MB, Warren TH, Fales HM and Gottesman MM: Synthesis and structure-activity evaluation of isatin-β-thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein. J Med Chem. 54:5878–5889. 2011.

28 

Huang C, Xu D, Xia Q, Wang P, Rong C and Su Y: Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II. J Pharm Pharmacol. 64:1741–1750. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Yan F, Wang XM, Liu ZC, Pan C, Yuan SB and Ma QM: JNK1, JNK2, and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells. Hepatobiliary Pancreat Dis Int. 9:287–295. 2010.PubMed/NCBI

30 

Eicher C, Dewerth A, Kirchner B, Warmann SW, Fuchs J and Armeanu-Ebinger S: Development of a drug resistance model for hepatoblastoma. Int J Oncol. 38:447–454. 2010.PubMed/NCBI

31 

Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Barrand MA, Heppell-Parton AC, Wright KA, Rabbitts PH and Twentyman PR: A 190-kilodalton protein overexpressed in non-P-glycoprotein-containing multidrug-resistant cells and its relationship to the MRP gene. J Natl Cancer Inst. 86:110–117. 1994. View Article : Google Scholar

33 

Mehta K: High levels of transglutaminase expression in doxorubicin-resistant human breast carcinoma cells. Int J Cancer. 58:400–406. 1994. View Article : Google Scholar : PubMed/NCBI

34 

Tong JS, Zhang QH, Huang X, Fu XQ, Qi ST, Wang YP, Hou Y, Sheng J and Sun QY: Icaritin causes sustained ERK1/2 activation and induces apoptosis in human endometrial cancer cells. PLoS One. 6:e167812011. View Article : Google Scholar : PubMed/NCBI

35 

Borst P and Schinkel AH: What have we learnt thus far from mice with disrupted P-glycoprotein genes? Eur J Cancer. 32:985–990. 1996. View Article : Google Scholar : PubMed/NCBI

36 

Kumar YS, Adukondalu D, Sathish D, Vishnu YV, Ramesh G, Latha AB, Reddy PC, Sarangapani M and Rao YM: P-Glycoprotein- and cytochrome P-450-mediated herbal drug interactions. Drug Metabol Drug Interact. 25:3–16. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sun L, Chen W, Qu L, Wu J and Si J: Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression. Mol Med Rep 8: 1883-1887, 2013.
APA
Sun, L., Chen, W., Qu, L., Wu, J., & Si, J. (2013). Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression. Molecular Medicine Reports, 8, 1883-1887. https://doi.org/10.3892/mmr.2013.1742
MLA
Sun, L., Chen, W., Qu, L., Wu, J., Si, J."Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression". Molecular Medicine Reports 8.6 (2013): 1883-1887.
Chicago
Sun, L., Chen, W., Qu, L., Wu, J., Si, J."Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression". Molecular Medicine Reports 8, no. 6 (2013): 1883-1887. https://doi.org/10.3892/mmr.2013.1742
Copy and paste a formatted citation
x
Spandidos Publications style
Sun L, Chen W, Qu L, Wu J and Si J: Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression. Mol Med Rep 8: 1883-1887, 2013.
APA
Sun, L., Chen, W., Qu, L., Wu, J., & Si, J. (2013). Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression. Molecular Medicine Reports, 8, 1883-1887. https://doi.org/10.3892/mmr.2013.1742
MLA
Sun, L., Chen, W., Qu, L., Wu, J., Si, J."Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression". Molecular Medicine Reports 8.6 (2013): 1883-1887.
Chicago
Sun, L., Chen, W., Qu, L., Wu, J., Si, J."Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression". Molecular Medicine Reports 8, no. 6 (2013): 1883-1887. https://doi.org/10.3892/mmr.2013.1742
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team