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-2015 Volume 34 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-2015 Volume 34 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 Open Access

Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer

  • Authors:
    • Yuefeng Du
    • Qingzhi Long
    • Ying Shi
    • Xiaogang Liu
    • Xudong Li
    • Jin Zeng
    • Yongguang Gong
    • Lei Li
    • Xinyang Wang
    • Dalin He
  • View Affiliations / Copyright

    Affiliations: Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Urology, Tongji Medical College Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China, School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2273-2281
    |
    Published online on: August 13, 2015
       https://doi.org/10.3892/or.2015.4201
  • 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

IGF-binding protein-3 (IGFBP-3) has been shown to induce apoptosis in an insulin-like growth factor (IGF)‑independent manner in various cell systems, however, the underlying molecular mechanisms remain unknown. In the present study, we showed that IGFBP-3 significantly enhanced interleukin-24 (IL-24)-induced cell death in prostate cancer (PC) cell lines in vitro. Both the addition of IGFBP-3 to cell medium or the enforced expression of IGFBP-3 in the PC cell line inhibited activation of mammalian target of rapamycin (mTOR). Downregulation of mTOR/S6K reduced Mcl-1 protein expression and consequently promoted sensitization to IL-24 treatment. Overexpression of Mcl-1 reduced the level of cleaved poly(ADP-ribose) polymerase (PARP) induced by IL-24 and IGFBP-3, suggesting that the IL-24-induced apoptosis is realized by way of Mcl-1. We then showed that the combination of IL-24 and IGFBP-3 significantly suppressed PC tumor growth in vivo. We propose that the IGFBP-3 and IL-24 non-toxic mTOR inhibitors can be used as an adjuvant in the treatment of PC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Gill ZP, Perks CM, Newcomb PV and Holly JM: Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem. 272:25602–25607. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Nakamura M, Takakura M, Fujii R, Maida Y, Bono Y, Mizumoto Y, Zhang X, Kiyono T and Kyo S: The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth. Cancer Lett. 336:68–75. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Hanafusa T, Shinji T, Shiraha H, Nouso K, Iwasaki Y, Yumoto E, Ono T and Koide N: Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation. BMC Cancer. 5:92005. View Article : Google Scholar : PubMed/NCBI

4 

Baxter RC, Butt AJ, Schedlich LJ and Martin JL: Antiproliferative and pro-apoptotic activities of insulin-like growth factor-binding protein-3. Growth Horm IGF Res. 10(10 Suppl A): S10–S11. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Ho L, Stojanovski A, Whetstone H, Wei QX, Mau E, Wunder JS and Alman B: Gli2 and p53 cooperate to regulate IGFBP-3-mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors. Cancer Cell. 16:126–136. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Butt AJ and Williams AC: IGFBP-3 and apoptosis - a license to kill? Apoptosis. 6:199–205. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Williams AC, Collard TJ, Perks CM, Newcomb P, Moorghen M, Holly JM and Paraskeva C: Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res. 60:22–27. 2000.PubMed/NCBI

8 

Hollowood AD, Lai T, Perks CM, Newcomb PV, Alderson D and Holly JM: IGFBP-3 prolongs the p53 response and enhances apoptosis following UV irradiation. Int J Cancer. 88:336–341. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Collard TJ, Guy M, Butt AJ, Perks CM, Holly JM, Paraskeva C and Williams AC: Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells. Carcinogenesis. 24:393–401. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, Kang D, Jiang H, Lin JJ, Alexandre D, et al: Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene. 20:7051–7063. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Ellerhorst JA, Prieto VG, Ekmekcioglu S, Broemeling L, Yekell S, Chada S and Grimm EA: Loss of MDA-7 expression with progression of melanoma. J Clin Oncol. 20:1069–1074. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Chada S, Sutton RB, Ekmekcioglu S, Ellerhorst J, Mumm JB, Leitner WW, Yang HY, Sahin AA, Hunt KK, Fuson KL, et al: MDA-7/IL-24 is a unique cytokine - tumor suppressor in the IL-10 family. Int Immunopharmacol. 4:649–667. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Dent P, Yacoub A, Hamed HA, Park MA, Dash R, Bhutia SK, Sarkar D, Wang XY, Gupta P, Emdad L, et al: The development of MDA-7/IL-24 as a cancer therapeutic. Pharmacol Ther. 128:375–384. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Xu S, Oshima T, Imada T, Masuda M, Debnath B, Grande F, Garofalo A and Neamati N: Stabilization of MDA-7/IL-24 for colon cancer therapy. Cancer Lett. 335:421–430. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Gupta P, Emdad L, Lebedeva IV, Sarkar D, Dent P, Curiel DT, Settleman J and Fisher PB: Targeted combinatorial therapy of non-small cell lung carcinoma using a GST-fusion protein of full-length or truncated MDA-7/IL-24 with Tarceva. J Cell Physiol. 215:827–836. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Deng WG, Kwon J, Ekmekcioglu S, Poindexter NJ and Grimm EA: IL-24 gene transfer sensitizes melanoma cells to erlotinib through modulation of the Apaf-1 and Akt signaling pathways. Melanoma Res. 21:44–56. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Sauane M, Gopalkrishnan RV, Sarkar D, Su ZZ, Lebedeva IV, Dent P, Pestka S and Fisher PB: MDA-7/IL-24: Novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev. 14:35–51. 2003. View Article : Google Scholar

18 

Mhashilkar AM, Schrock RD, Hindi M, Liao J, Sieger K, Kourouma F, Zou-Yang XH, Onishi E, Takh O, Vedvick TS, et al: Melanoma differentiation associated gene-7 (mda-7): A novel anti-tumor gene for cancer gene therapy. Mol Med. 7:271–282. 2001.PubMed/NCBI

19 

Chada S, Mhashilkar AM, Liu Y, Nishikawa T, Bocangel D, Zheng M, Vorburger SA, Pataer A, Swisher SG, Ramesh R, et al: mda-7 gene transfer sensitizes breast carcinoma cells to chemotherapy, biologic therapies and radiotherapy: Correlation with expression of bcl-2 family members. Cancer Gene Ther. 13:490–502. 2006. View Article : Google Scholar

20 

Lebedeva IV, Sarkar D, Su ZZ, Kitada S, Dent P, Stein CA, Reed JC and Fisher PB: Bcl-2 and Bcl-xL differentially protect human prostate cancer cells from induction of apoptosis by melanoma differentiation associated gene-7, mda-7/IL-24. Oncogene. 22:8758–8773. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Ma XM and Blenis J: Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 10:307–318. 2009. View Article : Google Scholar : PubMed/NCBI

22 

She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit DB and Rosen N: 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell. 18:39–51. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 441:424–430. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Cusack JC Jr: Overcoming antiapoptotic responses to promote chemosensitivity in metastatic colorectal cancer to the liver. Ann Surg Oncol. 10:852–862. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Fabbri F, Brigliadori G, Carloni S, Ulivi P, Vannini I, Tesei A, Silvestrini R, Amadori D and Zoli W: Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line. J Transl Med. 6:432008. View Article : Google Scholar : PubMed/NCBI

26 

Mills JR, Hippo Y, Robert F, Chen SM, Malina A, Lin CJ, Trojahn U, Wendel HG, Charest A, Bronson RT, et al: mTORC1 promotes survival through translational control of Mcl-1. Proc Natl Acad Sci USA. 105:10853–10858. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Chan S: Targeting the mammalian target of rapamycin (mTOR): A new approach to treating cancer. Br J Cancer. 91:1420–1424. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Petroulakis E, Mamane Y, Le Bacquer O, Shahbazian D and Sonenberg N: mTOR signaling: Implications for cancer and anticancer therapy. Br J Cancer. 96(Suppl): R11–R15. 2007.PubMed/NCBI

29 

Adams JM: Ways of dying: Multiple pathways to apoptosis. Genes Dev. 17:2481–2495. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Du Y, Long Q, Shi Y, Liu X, Li X, Zeng J, Gong Y, Li L, Wang X, He D, He D, et al: Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer. Oncol Rep 34: 2273-2281, 2015.
APA
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J. ... He, D. (2015). Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer. Oncology Reports, 34, 2273-2281. https://doi.org/10.3892/or.2015.4201
MLA
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J., Gong, Y., Li, L., Wang, X., He, D."Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer". Oncology Reports 34.5 (2015): 2273-2281.
Chicago
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J., Gong, Y., Li, L., Wang, X., He, D."Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer". Oncology Reports 34, no. 5 (2015): 2273-2281. https://doi.org/10.3892/or.2015.4201
Copy and paste a formatted citation
x
Spandidos Publications style
Du Y, Long Q, Shi Y, Liu X, Li X, Zeng J, Gong Y, Li L, Wang X, He D, He D, et al: Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer. Oncol Rep 34: 2273-2281, 2015.
APA
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J. ... He, D. (2015). Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer. Oncology Reports, 34, 2273-2281. https://doi.org/10.3892/or.2015.4201
MLA
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J., Gong, Y., Li, L., Wang, X., He, D."Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer". Oncology Reports 34.5 (2015): 2273-2281.
Chicago
Du, Y., Long, Q., Shi, Y., Liu, X., Li, X., Zeng, J., Gong, Y., Li, L., Wang, X., He, D."Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer". Oncology Reports 34, no. 5 (2015): 2273-2281. https://doi.org/10.3892/or.2015.4201
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