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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
2014-April Volume 31 Issue 4

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
2014-April Volume 31 Issue 4

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

Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways

  • Authors:
    • Yang Dong
    • Aili Cao
    • Jianrong Shi
    • Peihao Yin
    • Li Wang
    • Guang Ji
    • Jianqun Xie
    • Dazheng Wu
  • View Affiliations / Copyright

    Affiliations: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
  • Pages: 1788-1794
    |
    Published online on: February 19, 2014
       https://doi.org/10.3892/or.2014.3034
  • 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

Tangeretin, a natural polymethoxyflavone present in citrus peel oil, is known to have anticancer activities in breast cancer, colorectal carcinoma and lung carcinoma, yet, the underlying mechanisms of tangeretin in human gastric cancer AGS cells have not been investigated to date. In the present study, the apoptotic mechanisms of tangeretin in AGS cells were explored. It was observed that tangeretin increased the apoptotic rates of AGS cells following treatment with tangeretin for 48 h in a dose-dependent manner by Annexin V-FITC and PI double staining. In addition, characteristic apoptotic morphology such as nuclear shrinkage and apoptotic bodies was observed after Hoechst 33258 staining. Flow cytometric assay showed that treatment of AGS cells with tangeretin decreased the mitochondrial membrane potential (MMP) in a dose-dependent manner, which indicated that mitochondrial dysfunction was involved in the tangeretin-induced apoptosis. Caspase-3, -8 and -9 activities were increased by tangeretin in a dose-dependent manner. Western blotting showed that the protein levels of pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, Bid, tBid, p53, p21/cip1, Fas and FasL were significantly upregulated by tangeretin. In addition, PFT-α (a p53 inhibitor) reduced the apoptotic rates and the expression of p53, p21, caspase-3 and caspase-9 induced by tangeretin, indicating that tangeretin-induced apoptosis was p53-dependent. In conclusion, these results suggest that tangeretin induces the apoptosis of AGS cells mainly through p53-dependent mitochondrial dysfunction and the Fas/FasL-mediated extrinsic pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Wang D, Wang J, Huang X, Tu Y and Ni K: Identification of polymethoxylated flavones from green tangerine peel (Pericarpium Citri Reticulatae Viride) by chromatographic and spectroscopic techniques. J Pharm Biomed Anal. 44:63–69. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Hirano T, Abe K, Gotoh M and Oka K: Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. Br J Cancer. 72:1380–1388. 1995. View Article : Google Scholar : PubMed/NCBI

3 

Rooprai HK, Kandanearatchi A, Maidment SL, et al: Evaluation of the effects of swainsonine, captopril, tangeretin and nobiletin on the biological behaviour of brain tumour cells in vitro. Neuropathol Appl Neurobiol. 27:29–39. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Martinez Conesa C, Vicente Ortega V, Yanez Gascon MJ, et al: Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin. J Agric Food Chem. 53:6791–6797. 2005.PubMed/NCBI

5 

Manthey JA and Guthrie N: Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J Agric Food Chem. 50:5837–5843. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Ishii K, Tanaka S, Kagami K, et al: Effects of naturally occurring polymethyoxyflavonoids on cell growth, P-glycoprotein function, cell cycle, and apoptosis of daunorubicin-resistant T lymphoblastoid leukemia cells. Cancer Invest. 28:220–229. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Morley KL, Ferguson PJ and Koropatnick J: Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett. 251:168–178. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Pan MH, Chen WJ, Lin-Shiau SY, Ho CT and Lin JK: Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells. Carcinogenesis. 23:1677–1684. 2002. View Article : Google Scholar

9 

Chen KH, Weng MS and Lin JK: Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells. Biochem Pharmacol. 73:215–227. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Lust S, Vanhoecke B, Van Gele M, Philippe J, Bracke M and Offner F: The flavonoid tangeretin activates the unfolded protein response and synergizes with imatinib in the erythroleukemia cell line K562. Mol Nutr Food Res. 54:823–832. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Arafa el SA, Zhu Q, Barakat BM, et al: Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway. Cancer Res. 69:8910–8917. 2009.PubMed/NCBI

12 

Gao J, Senthil M, Ren B, et al: IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial apoptotic pathway in IRF-1-induced apoptosis in cancer cells. Cell Death Differ. 17:699–709. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Jiang XH, Wong BC, Lin MC, et al: Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cells. Oncogene. 20:8009–8018. 2001.PubMed/NCBI

14 

Linke SP, Clarkin KC and Wahl GM: p53 mediates permanent arrest over multiple cell cycles in response to γ-irradiation. Cancer Res. 57:1171–1179. 1997.PubMed/NCBI

15 

Midgley CA, Owens B, Briscoe CV, Thomas DB, Lane DP and Hall PA: Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo. J Cell Sci. 108:1843–1848. 1995.PubMed/NCBI

16 

Goldstein I, Marcel V, Olivier M, Oren M, Rotter V and Hainaut P: Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer Gene Ther. 18:2–11. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Dong Y, Ji G, Shi JR, Cao AL, Xie JQ and Wu DZ: Arrest of human gastric cancer AGS cells by tangeretin via cyclinB1 upregulation and inhibition of ERK phosphorylation. Chin Pharmacol Bull. 28:52012.

18 

Cohen GM: Caspases: the executioners of apoptosis. Biochem J. 326:1–16. 1997.

19 

Budihardjo I, Oliver H, Lutter M, Luo X and Wang X: Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 15:269–290. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Dias N and Bailly C: Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol. 70:1–12. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S and Peter ME: Apoptosis signaling by death receptors. Eur J Biochem. 254:439–459. 1998. View Article : Google Scholar

22 

Rao RV, Ellerby HM and Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11:372–380. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Zamzami N, Marchetti P, Castedo M, et al: Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med. 182:367–377. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Zamzami N, Marchetti P, Castedo M, et al: Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med. 181:1661–1672. 1995. View Article : Google Scholar : PubMed/NCBI

25 

Kudla G, Montessuit S, Eskes R, et al: The destabilization of lipid membranes induced by the C-terminal fragment of caspase 8-cleaved bid is inhibited by the N-terminal fragment. J Biol Chem. 275:22713–22718. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Roucou X, Montessuit S, Antonsson B and Martinou JC: Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein. Biochem J. 368:915–921. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM and Gottlieb E: BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ. 18:538–548. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Vousden KH and Lu X: Live or let die: the cell’s response to p53. Nat Rev Cancer. 2:594–604. 2002.

29 

Cui Q, Yu JH, Wu JN, et al: P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells. Acta Pharmacol Sin. 28:1057–1066. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Lu L, Dong Y, Shi JR and Wu DZ: Tangeretin enhances the proliferation inhibition of 5-fluorouracil in human gastric cancer AGS cells. Chin Pharmacol Bull. 27:760–763. 2011.

31 

Bunz F, Dutriaux A, Lengauer C, et al: Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 282:1497–1501. 1998. View Article : Google Scholar : PubMed/NCBI

32 

Kurland JF and Meyn RE: Protease inhibitors restore radiation-induced apoptosis to Bcl-2-expressing lymphoma cells. Int J Cancer. 96:327–333. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Dong Y, Cao A, Shi J, Yin P, Wang L, Ji G, Xie J and Wu D: Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways. Oncol Rep 31: 1788-1794, 2014.
APA
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G. ... Wu, D. (2014). Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways. Oncology Reports, 31, 1788-1794. https://doi.org/10.3892/or.2014.3034
MLA
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G., Xie, J., Wu, D."Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways". Oncology Reports 31.4 (2014): 1788-1794.
Chicago
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G., Xie, J., Wu, D."Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways". Oncology Reports 31, no. 4 (2014): 1788-1794. https://doi.org/10.3892/or.2014.3034
Copy and paste a formatted citation
x
Spandidos Publications style
Dong Y, Cao A, Shi J, Yin P, Wang L, Ji G, Xie J and Wu D: Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways. Oncol Rep 31: 1788-1794, 2014.
APA
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G. ... Wu, D. (2014). Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways. Oncology Reports, 31, 1788-1794. https://doi.org/10.3892/or.2014.3034
MLA
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G., Xie, J., Wu, D."Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways". Oncology Reports 31.4 (2014): 1788-1794.
Chicago
Dong, Y., Cao, A., Shi, J., Yin, P., Wang, L., Ji, G., Xie, J., Wu, D."Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways". Oncology Reports 31, no. 4 (2014): 1788-1794. https://doi.org/10.3892/or.2014.3034
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