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-March Volume 31 Issue 3

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-March Volume 31 Issue 3

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

Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling

  • Authors:
    • Wenbin Song
    • Qiang Dang
    • Defeng Xu
    • Yule Chen
    • Guodong Zhu
    • Kaijie Wu
    • Jin Zeng
    • Qingzhi Long
    • Xinyang Wang
    • Dalin He
    • Lei Li
  • View Affiliations / Copyright

    Affiliations: Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China
  • Pages: 1350-1356
    |
    Published online on: January 7, 2014
       https://doi.org/10.3892/or.2014.2965
  • 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

Kaempferol has been shown to inhibit cell growth, induce apoptosis and cell cycle arrest in several tumors, but not in renal cell carcinoma (RCC). In the present study, we investigated the effects of kaempferol and the underlying mechanism(s) on the cell growth of RCC cells. MTT assay and colony formation assay were used to study cell growth, and flow cytometry was used to study apoptosis and cell cycles in different RCC cells treated with various doses of kaempferol. A significant inhibition on cell growth, induction of apoptosis and cell cycle arrest were observed in 786-O and 769-P cells after kaempferol treatment compared with the control group. Moreover, the results clearly showed that kaempferol causes a strong inhibition of the activation of the EGFR/p38 signaling pathways, upregulation of p21 expression and downregulation of cyclin B1 expression in human RCC cells, together with activation of PARP cleavages, induction of apoptotic death and inhibition of cell growth. Collectively, our results suggest that kaempferol may serve as a candidate for chemo­preventive or chemotherapeutic agents for RCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Cohen HT and McGovern FJ: Renal-cell carcinoma. N Engl J Med. 353:2477–2490. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Yagoda A, Abi-Rached B and Petrylak D: Chemotherapy for advanced renal-cell carcinoma: 1983–1993. Semin Oncol. 22:42–60. 1995.

3 

Li L, Gao Y, Zhang L, Zeng J, He D and Sun Y: Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma. Cancer Lett. 272:61–69. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Bex A, Kerst M, Mallo H, Meinhardt W, Horenblas S and de Gast GC: Interferon alpha 2b as medical selection for nephrectomy in patients with synchronous metastatic renal cell carcinoma: a consecutive study. Eur Urol. 49:76–81. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Calderón-Montaño JM, Burgos-Morón E, Pérez-Guerrero C and López-Lázaro M: A review on the dietary flavonoid kaempferol. Mini Rev Med Chem. 11:298–344. 2011.PubMed/NCBI

6 

Cui Y, Morgenstern H, Greenland S, et al: Dietary flavonoid intake and lung cancer - a population-based case-control study. Cancer. 112:2241–2248. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Nothlings U, Murphy SP, Wilkens LR, Henderson BE and Kolonel LN: Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am J Epidemiol. 166:924–931. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B and Hankinson SE: A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer. 121:2225–2232. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Luo H, Daddysman MK, Rankin GO, Jiang BH and Chen YC: Kaempferol enhances cisplatin’s effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc. Cancer Cell Int. 10:162010.PubMed/NCBI

10 

Kang JW, Kim JH, Song K, Kim SH, Yoon JH and Kim KS: Kaempferol and Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase-3-dependent apoptosis in oral cavity cancer cells. Phytother Res. 24(Suppl 1): S77–S82. 2010.PubMed/NCBI

11 

Huang WW, Chiu YJ, Fan MJ, et al: Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res. 54:1585–1595. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Li W, Du B, Wang T, Wang S and Zhang J: Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-Telangiectasia Mutated-p53 pathway with the involvement of p53 Upregulated Modulator of Apoptosis. Chem Biol Interact. 177:121–127. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Qin W, Lei Y-H, Su M, Li D-J, Zhang N and Shen Y-Q: Kaempferol inhibits proliferation of human prostate cancer PC-3 cells via down-regulation of PCNA and VCAM-1. Zhongguo Yaolixue Tongbao. 27:553–557. 2011.(In Chinese).

14 

Ahn MR, Kunimasa K, Kumazawa S, et al: Correlation between antiangiogenic activity and antioxidant activity of various components from propolis. Mol Nutr Food Res. 53:643–651. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Schindler R and Mentlein R: Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr. 136:1477–1482. 2006.PubMed/NCBI

16 

Shin MS, Shinghirunnusorn P, Sugishima Y, et al: Cross interference with TNF-alpha-induced TAK1 activation via EGFR-mediated p38 phosphorylation of TAK1-binding protein 1. Biochim Biophys Acta. 1793:1156–1164. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Cohen D, Lane B, Jin T, et al: The prognostic significance of epidermal growth factor receptor expression in clear-cell renal cell carcinoma: a call for standardized methods for immunohistochemical evaluation. Clin Genitourin Cancer. 5:264–270. 2007. View Article : Google Scholar

18 

Badalian G, Derecskei K, Szendroi A, Szendroi M and Timar J: EGFR and VEGFR2 protein expressions in bone metastases of clear cell renal cancer. Anticancer Res. 27:889–894. 2007.PubMed/NCBI

19 

Fanger GR, Johnson NL and Johnson GL: MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42. EMBO J. 16:4961–4972. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Marshall CJ: Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 80:179–185. 1995. View Article : Google Scholar

21 

Han Y, Caday CG, Nanda A, Cavenee WK and Huang HJ: Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors. Cancer Res. 56:3859–3861. 1996.PubMed/NCBI

22 

Clerk A and Sugden PH: The p38-MAPK inhibitor, SB203580, inhibits cardiac stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs). FEBS Lett. 426:93–96. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Labbe D, Provencal M, Lamy S, Boivin D, Gingras D and Beliveau R: The flavonols quercetin, kaempferol, and myricetin inhibit hepatocyte growth factor-induced medulloblastoma cell migration. J Nutr. 139:646–652. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Nguyen TTT, Tran E, Ong CK, et al: Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol. 197:110–121. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Malumbres M and Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 9:153–166. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Huang WW, Tsai SC, Peng SF, et al: Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells. Int J Oncol. 42:2069–2077. 2013.PubMed/NCBI

27 

Naowaratwattana W, De-Eknamkul W and De Mejia EG: Phenolic-containing organic extracts of mulberry (Morus alba L.) leaves inhibit HepG2 hepatoma cells through G2/M phase arrest, induction of apoptosis, and inhibition of topoisomerase IIα activity. J Med Food. 13:1045–1056. 2010.PubMed/NCBI

28 

Zhang Q, Zhao XH and Wang ZJ: Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 23:797–807. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Mu JJ, Zeng YY, Huang XY, Zhao XH and Song B: Effects of Kaempferol on activation, proliferation and cell cycle of mouse T lymphocytes in vitro. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 25:1106–1108. 2009.(In Chinese).

30 

Eto M and Naito S: Molecular targeting therapy for renal cell carcinoma. Int J Clin Oncol. 11:209–213. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Staehler M, Rohrmann K, Haseke N, Stief CG and Siebels M: Targeted agents for the treatment of advanced renal cell carcinoma. Curr Drug Targets. 6:835–846. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Zhang LJ, Chen S, Wu P, et al: Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric cancer cells. Cancer Lett. 274:40–46. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Oda K, Matsuoka Y, Funahashi A and Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 1:2005.00102005.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Song W, Dang Q, Xu D, Chen Y, Zhu G, Wu K, Zeng J, Long Q, Wang X, He D, He D, et al: Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling. Oncol Rep 31: 1350-1356, 2014.
APA
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K. ... Li, L. (2014). Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling. Oncology Reports, 31, 1350-1356. https://doi.org/10.3892/or.2014.2965
MLA
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K., Zeng, J., Long, Q., Wang, X., He, D., Li, L."Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling". Oncology Reports 31.3 (2014): 1350-1356.
Chicago
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K., Zeng, J., Long, Q., Wang, X., He, D., Li, L."Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling". Oncology Reports 31, no. 3 (2014): 1350-1356. https://doi.org/10.3892/or.2014.2965
Copy and paste a formatted citation
x
Spandidos Publications style
Song W, Dang Q, Xu D, Chen Y, Zhu G, Wu K, Zeng J, Long Q, Wang X, He D, He D, et al: Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling. Oncol Rep 31: 1350-1356, 2014.
APA
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K. ... Li, L. (2014). Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling. Oncology Reports, 31, 1350-1356. https://doi.org/10.3892/or.2014.2965
MLA
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K., Zeng, J., Long, Q., Wang, X., He, D., Li, L."Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling". Oncology Reports 31.3 (2014): 1350-1356.
Chicago
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K., Zeng, J., Long, Q., Wang, X., He, D., Li, L."Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling". Oncology Reports 31, no. 3 (2014): 1350-1356. https://doi.org/10.3892/or.2014.2965
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