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
November-2014 Volume 32 Issue 5

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
November-2014 Volume 32 Issue 5

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

Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87

  • Authors:
    • Yubao Zhang
    • Xia Ren
    • Meiyan Shi
    • Zheng  Jiang
    • Hengxiao  Wang
    • Qinghong Su
    • Qinglin Liu
    • Gang Li
    • Guosheng Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China, Key Laboratory for Rare and Uncommon Diseases, Key Laboratory for Tumor Immunology and Chinese Medicine Immunology of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China
  • Pages: 2038-2046
    |
    Published online on: August 22, 2014
       https://doi.org/10.3892/or.2014.3434
  • 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

Honokiol [3,5-di-(2-propenyl)-1,1-biphenyl-2,2-diol; HNK], a natural bioactive molecular compound isolated from the Magnolia officinalis, exhibits potent antitumor activity against a variety of human cancer cell lines. However, few studies have reported the antineoplastic effects of HNK on glioblastoma cells. It remains unknown how apoptosis is induced by HNK in glioblastoma cells and through which associated pathway this compound acts. The present study confirmed that HNK inhibited proliferation of glioblastoma cells by inducing a slight G0/G1 phase cell cycle arrest and apoptosis. We demonstrated for the first time that HNK triggered apoptosis of glioblastoma cells through both caspase-independent and caspase-dependent pathways, the latter including the extrinsic pathway and intrinsic pathway. Moreover, the inhibition of STAT3 signaling, ERK1/2 as well as activation of the p38 MAPK signaling pathway may be involved in apoptosis induced by HNK in U87 cells. Our findings suggest that HNK treatment could be a promising therapeutic strategy in human glioblastoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Dolecek TA, Propp JM, Stroup NE and Kruchko C: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol. 14(Suppl 5): v1–v49. 2012.PubMed/NCBI

2 

Gauden AJ, Hunn A, Erasmus A, Waites P, Dubey A and Gauden SJ: Combined modality treatment of newly diagnosed glioblastoma multiforme in a regional neurosurgical centre. J Clin Neurosci. 16:1174–1179. 2009. View Article : Google Scholar

3 

Jansen M, Yip S and Louis DN: Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol. 9:717–726. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Arora S, Singh S, Piazza GA, Contreras CM, Panyam J and Singh AP: Honokiol: a novel natural agent for cancer prevention and therapy. Curr Mol Med. 12:1244–1252. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Ishikawa C, Arbiser JL and Mori N: Honokiol induces cell cycle arrest and apoptosis via inhibition of survival signals in adult T-cell leukemia. Biochim Biophys Acta. 1820:879–887. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Wang T, Chen F, Chen Z, Wu YF, Xu XL, Zheng S and Hu X: Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol. 10:2205–2208. 2004.PubMed/NCBI

7 

Arora S, Bhardwaj A, Srivastava SK, Singh S, McClellan S, Wang B and Singh AP: Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One. 6:e215732011. View Article : Google Scholar : PubMed/NCBI

8 

Wolf I, O’Kelly J, Wakimoto N, et al: Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. Int J Oncol. 30:1529–1537. 2007.

9 

Hahm ER and Singh SV: Honokiol causes G0–G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Mol Cancer Ther. 6:2686–2695. 2007.

10 

Wang Y, Yang Z and Zhao X: Honokiol induces paraptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells. Toxicol Mech Methods. 20:234–241. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Kaushik G, Ramalingam S, Subramaniam D, et al: Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells. Am J Surg. 204:868–873. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Wang X, Duan X, Yang G, et al: Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PLoS One. 6:e184902011. View Article : Google Scholar : PubMed/NCBI

13 

Jeong JJ, Lee JH, Chang KC and Kim HJ: Honokiol exerts an anticancer effect in T98G human glioblastoma cells through the induction of apoptosis and the regulation of adhesion molecules. Int J Oncol. 41:1358–1364. 2012.

14 

Ren X, Zhang Y, Li C, et al: Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells. Oncol Rep. 30:2071–2080. 2013.

15 

Liu J, Bi G, Wen P, et al: Down-regulation of CD44 contributes to the differentiation of HL-60 cells induced by ATRA or HMBA. Cell Mol Immunol. 4:59–63. 2007.PubMed/NCBI

16 

Riedl SJ and Shi Y: Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 5:897–907. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Shimizu S, Narita M and Tsujimoto Y: Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 399:483–487. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Ishitsuka K, Hideshima T, Hamasaki M, et al: Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood. 106:1794–1800. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA and Haque SJ: Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene. 21:8404–8413. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Yu H and Jove R: The STATs of cancer - new molecular targets come of age. Nat Rev Cancer. 4:97–105. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Zhou J, Bi C, Janakakumara JV, et al: Enhanced activation of STAT pathways and overexpression of survivin confer resistance to FLT3 inhibitors and could be therapeutic targets in AML. Blood. 113:4052–4062. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM and Pagano M: Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol. 15:2612–2624. 1995.PubMed/NCBI

23 

Ullah Z, Lee CY and Depamphilis ML: Cip/Kip cyclin-dependent protein kinase inhibitors and the road to polyploidy. Cell Div. 4:102009. View Article : Google Scholar : PubMed/NCBI

24 

Constantinou C, Papas KA and Constantinou AI: Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy? Curr Cancer Drug Targets. 9:717–728. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Battle TE, Arbiser J and Frank DA: The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 106:690–697. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Desagher S and Martinou JC: Mitochondria as the central control point of apoptosis. Trends Cell Biol. 10:369–377. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Reed JC, Jurgensmeier JM and Matsuyama S: Bcl-2 family proteins and mitochondria. Biochim Biophys Acta. 1366:127–137. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Ramos S: Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol Nutr Food Res. 52:507–526. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Zhang W and Liu HT: MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 12:9–18. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Glassmann A, Reichmann K, Scheffler B, Glas M, Veit N and Probstmeier R: Pharmacological targeting of the constitutively activated MEK/MAPK-dependent signaling pathway in glioma cells inhibits cell proliferation and migration. Int J Oncol. 39:1567–1575. 2011.PubMed/NCBI

31 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

32 

Qiao S, Murakami K, Zhao Q, et al: Mimosine-induced apoptosis in C6 glioma cells requires the release of mitochondria-derived reactive oxygen species and p38, JNK activation. Neurochem Res. 37:417–427. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Sharma V, Koul N, Joseph C, Dixit D, Ghosh S and Sen E: HDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation and inhibits telomerase activity. J Cell Mol Med. 14:2151–2161. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Huh JE, Kang KS, Chae C, Kim HM, Ahn KS and Kim SH: Roles of p38 and JNK mitogen-activated protein kinase pathways during cantharidin-induced apoptosis in U937 cells. Biochem Pharmacol. 67:1811–1818. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Konopleva M, Contractor R, Kurinna SM, Chen W, Andreeff M and Ruvolo PP: The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells. Leukemia. 19:1350–1354. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Han LL, Xie LP, Li LH, Zhang XW, Zhang RQ and Wang HZ: Reactive oxygen species production and Bax/Bcl-2 regulation in honokiol-induced apoptosis in human hepatocellular carcinoma SMMC-7721 cells. Environ Toxicol Pharmacol. 28:97–103. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Stearns D, Chaudhry A, Abel TW, Burger PC, Dang CV and Eberhart CG: c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 66:673–681. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Gu J, Li G, Sun T, et al: Blockage of the STAT3 signaling pathway with a decoy oligonucleotide suppresses growth of human malignant glioma cells. J Neurooncol. 89:9–17. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Rajendran P, Li F, Shanmugam MK, et al: Honokiol inhibits signal transducer and activator of transcription-3 signaling, proliferation, and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J Cell Physiol. 227:2184–2195. 2012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Ren X, Shi M, Jiang Z, Wang H, Su Q, Liu Q, Li G and Jiang G: Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87. Oncol Rep 32: 2038-2046, 2014.
APA
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q. ... Jiang, G. (2014). Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87. Oncology Reports, 32, 2038-2046. https://doi.org/10.3892/or.2014.3434
MLA
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q., Liu, Q., Li, G., Jiang, G."Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87". Oncology Reports 32.5 (2014): 2038-2046.
Chicago
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q., Liu, Q., Li, G., Jiang, G."Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87". Oncology Reports 32, no. 5 (2014): 2038-2046. https://doi.org/10.3892/or.2014.3434
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Ren X, Shi M, Jiang Z, Wang H, Su Q, Liu Q, Li G and Jiang G: Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87. Oncol Rep 32: 2038-2046, 2014.
APA
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q. ... Jiang, G. (2014). Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87. Oncology Reports, 32, 2038-2046. https://doi.org/10.3892/or.2014.3434
MLA
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q., Liu, Q., Li, G., Jiang, G."Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87". Oncology Reports 32.5 (2014): 2038-2046.
Chicago
Zhang, Y., Ren, X., Shi, M., Jiang, Z., Wang, H., Su, Q., Liu, Q., Li, G., Jiang, G."Downregulation of STAT3 and activation of MAPK are involved in the induction of apoptosis by HNK in glioblastoma cell line U87". Oncology Reports 32, no. 5 (2014): 2038-2046. https://doi.org/10.3892/or.2014.3434
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