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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
February-2016 Volume 48 Issue 2

Full Size Image

Cover Legend PDF

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
February-2016 Volume 48 Issue 2

Full Size Image

Cover Legend PDF

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

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

  • Authors:
    • Lijie Ma
    • Ruixuan Wang
    • Yandong Nan
    • Wangping Li
    • Qingwei Wang
    • Faguang Jin
  • View Affiliations / Copyright

    Affiliations: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China
  • Pages: 843-853
    |
    Published online on: December 21, 2015
       https://doi.org/10.3892/ijo.2015.3304
  • 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

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dose-dependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

View References

1 

Subramaniam S, Thakur RK, Yadav VK, Nanda R, Chowdhury S and Agrawal A: Lung cancer biomarkers: State of the art. J Carcinog. 12:32013. View Article : Google Scholar : PubMed/NCBI

2 

Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L and Kunkler I; EUROCARE-4 Working Group. Recent cancer survival in Europe: A 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 8:784–796. 2007. View Article : Google Scholar : PubMed/NCBI

3 

de Boer A, Vos E and Bast A: Implementation of the nutrition and health claim regulation - the case of antioxidants. Regul Toxicol Pharmacol. 68:475–487. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Zicker SC, Wedekind KJ and Jewell DE: Antioxidants in veterinary nutrition. Vet Clin North Am Small Anim Pract. 36:1183–1198. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Mandel S, Amit T, Reznichenko L, Weinreb O and Youdim MB: Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Mol Nutr Food Res. 50:229–234. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Yang DS, Li ZL, Peng WB, Yang YP, Wang X, Liu KC, Li XL and Xiao WL: Three new prenylated flavonoids from Macaranga denticulata and their anticancer effects. Fitoterapia. 103:165–170. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Rezk BM, Haenen GR, van der Vijgh WJ and Bast A: The anti-oxidant activity of phloretin: The disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun. 295:9–13. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Zhang S and Morris ME: Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther. 304:1258–1267. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Pohl C, Will F, Dietrich H and Schrenk D: Cytochrome P450 1A1 expression and activity in Caco-2 cells: Modulation by apple juice extract and certain apple polyphenols. J Agric Food Chem. 54:10262–10268. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Nguyen H, Zhang S and Morris ME: Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J Pharm Sci. 92:250–257. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Boyer J and Liu RH: Apple phytochemicals and their health benefits. Nutr J. 3:52004. View Article : Google Scholar : PubMed/NCBI

12 

Kelly PN and Strasser A: The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 18:1414–1424. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Xin M and Deng X: Nicotine inactivation of the proapoptotic function of Bax through phosphorylation. J Biol Chem. 280:10781–10789. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Bayramoglu A, Gunes HV, Metintas M, Değirmenci I, Mutlu F and Alataş F: The association of MMP-9 enzyme activity, MMP-9 C1562T polymorphism, and MMP-2 and -9 and TIMP-1, -2, -3, and -4 gene expression in lung cancer. Genet Test Mol Biomarkers. 13:671–678. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Yang KC, Tsai CY, Wang YJ, Wei PL, Lee CH, Chen JH, Wu CH and Ho YS: Apple polyphenol phloretin potentiates the anticancer actions of paclitaxel through induction of apoptosis in human hep G2 cells. Mol Carcinog. 48:420–431. 2009. View Article : Google Scholar

16 

Nelson JA and Falk RE: Phloridzin and phloretin inhibition of 2-deoxy-D-glucose uptake by tumor cells in vitro and in vivo. Anticancer Res. 13A:2293–2299. 1993.

17 

Nelson JA and Falk RE: The efficacy of phloridzin and phloretin on tumor cell growth. Anticancer Res. 13A:2287–2292. 1993.

18 

Zhu SP, Liu G, Wu XT, Chen FX, Liu JQ, Zhou ZH, Zhang JF and Fei SJ: The effect of phloretin on human γδ T cells killing colon cancer SW-1116 cells. Int Immunopharmacol. 15:6–14. 2013. View Article : Google Scholar

19 

Karunagaran D, Joseph J and Kumar TR: Cell growth regulation. Adv Exp Med Biol. 595:245–268. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Rong Y and Distelhorst CW: Bcl-2 protein family members: Versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol. 70:73–91. 2008. View Article : Google Scholar

21 

Park HJ, Jeon YK, You DH and Nam MJ: Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells. Food Chem Toxicol. 60:542–549. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Fennell DA: Caspase regulation in non-small cell lung cancer and its potential for therapeutic exploitation. Clin Cancer Res. 11:2097–2105. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Balzer EM and Konstantopoulos K: Intercellular adhesion: Mechanisms for growth and metastasis of epithelial cancers. Wiley Interdiscip Rev Syst Biol Med. 4:171–181. 2012. View Article : Google Scholar

24 

Guruvayoorappan C and Kuttan G: Amentoflavone inhibits experimental tumor metastasis through a regulatory mechanism involving MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, STAT-1, NM23 and cytokines in lung tissues of C57BL/6 mice. Immunopharmacol Immunotoxicol. 30:711–727. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Chen RX, Xia YH, Xue TC, Zhang H and Ye SL: Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncol Rep. 25:803–808. 2011.

26 

Borkham-Kamphorst E, Alexi P, Tihaa L, Haas U and Weiskirchen R: Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities. Biochem Biophys Res Commun. 457:307–313. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Davis ME, Gumucio JP, Sugg KB, Bedi A and Mendias CL: MMP inhibition as a potential method to augment the healing of skeletal muscle and tendon extracellular matrix. J Appl Physiol. 115:884–891. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Wang R, Ke ZF, Wang F, Zhang WH, Wang YF, Li SH and Wang LT: GOLPH3 overexpression is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through upregulating MMP-2 and MMP-9. Cell Physiol Biochem. 35:969–982. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Xu X, Chen L, Xu B, Xie Q, Sun M, Deng X, Wu C and Jiang J: Increased MT2-MMP expression in gastric cancer patients is associated with poor prognosis. Int J Clin Exp Pathol. 8:1985–1990. 2015.PubMed/NCBI

30 

El-Badrawy MK, Yousef AM, Shaalan D and Elsamanoudy AZ: Matrix metalloproteinase-9 expression in lung cancer patients and its relation to serum MMP-9 activity, pathologic type, and prognosis. J Bronchol Interv Pulmonol. 21:327–334. 2014. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma L, Wang R, Nan Y, Li W, Wang Q and Jin F: Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. Int J Oncol 48: 843-853, 2016.
APA
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., & Jin, F. (2016). Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. International Journal of Oncology, 48, 843-853. https://doi.org/10.3892/ijo.2015.3304
MLA
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., Jin, F."Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases". International Journal of Oncology 48.2 (2016): 843-853.
Chicago
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., Jin, F."Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases". International Journal of Oncology 48, no. 2 (2016): 843-853. https://doi.org/10.3892/ijo.2015.3304
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Wang R, Nan Y, Li W, Wang Q and Jin F: Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. Int J Oncol 48: 843-853, 2016.
APA
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., & Jin, F. (2016). Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. International Journal of Oncology, 48, 843-853. https://doi.org/10.3892/ijo.2015.3304
MLA
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., Jin, F."Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases". International Journal of Oncology 48.2 (2016): 843-853.
Chicago
Ma, L., Wang, R., Nan, Y., Li, W., Wang, Q., Jin, F."Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases". International Journal of Oncology 48, no. 2 (2016): 843-853. https://doi.org/10.3892/ijo.2015.3304
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