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
January-2017 Volume 37 Issue 1

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
January-2017 Volume 37 Issue 1

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

Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70

  • Authors:
    • Yang Zhou
    • Jingping Ma
    • Jiahong Zhang
    • Li He
    • Jianhua Gong
    • Cong Long
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The Second Clinical Medical College, Yangtz University, Jingzhou, Hubei 434020, P.R. China, Department of Laboratory Medicine, Jingzhou First People's Hospital, Jingzhou, Hubei 434100, P.R. China
  • Pages: 313-322
    |
    Published online on: November 29, 2016
       https://doi.org/10.3892/or.2016.5286
  • 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

Heat-shock protein (Hsp) 70, known as a pro-survival protein, is aberrantly expressed in several malignancies. The small molecule 2-phenylethyenesulfonamide (PES), also referred to as pifithrin-μ, is known as an HSP70 inhibitor, which exhibits antitumor activities in a variety of cancer cell lines. However, little is known about its effect on non-small cell lung cancer (NSCLC) cell lines. This study aimed to investigate the effect of PES on human NSCLC cell lines A549 and H460, and explore the possible underlying mechanism of action. Cell viability assay by using CCK-8 kits was performed to demonstrate that PES dose- and time-dependently inhibited proliferation of A549 and H460 cells. Wound healing assay and Transwell migration assay results indicated that PES inhibited cell migration of A549 and H460 cells. Flow cytometry results demonstrated that PES resulted in G0/G1 phase cell cycle arrest, and induced apoptosis via a caspase-dependent manner in A549 and H460 cells. Western blotting results suggested that phosphorylation of AKT and ERK was inhibited by PES treatment. In addition, death receptor 4 (DR4) and DR5 were increased by PES treatment. Overexpression of Hsp70 in A549 cells attenuated the growth inhibitory efficiency of PES. Knockdown of Hsp70 in A549 cells enhanced sensitivity of PES to cell growth inhibition, suggesting that the inhibitory effect of PES on cell proliferation is specifically through Hsp70-dependent mechanism. PES and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a potent synergistic effect on cell proliferation inhibition and induction of apoptosis in A549 and H460 cells. In a mouse xenograft model of lung cancer by A549 cells, PES treatment displayed significant inhibitory effects on tumor growth. All these findings suggest that PES shows antitumor activity against human NSCLC in vitro and in vivo, and therefore may be a promising agent for use to the treatment of NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Erridge SC, Møller H, Price A and Brewster D: International comparisons of survival from lung cancer: Pitfalls and warnings. Nat Clin Pract Oncol. 4:570–577. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Jego G, Hazoumé A, Seigneuric R and Garrido C: Targeting heat shock proteins in cancer. Cancer Lett. 332:275–285. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Ritossa F: Discovery of the heat shock response. Cell Stress Chaperones. 1:97–98. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Wen W, Liu W, Shao Y and Chen L: VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity on lung cancer cell lines. Exp Biol Med (Maywood). 239:638–645. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Phillips PA, Dudeja V, McCarroll JA, Borja-Cacho D, Dawra RK, Grizzle WE, Vickers SM and Saluja AK: Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 67:9407–9416. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Suzuki K, Ito Y, Wakai K, Kawado M, Hashimoto S, Seki N, Ando M, Nishino Y, Kondo T, Watanabe Y, et al: Serum heat shock protein 70 levels and lung cancer risk: A case-control study nested in a large cohort study. Cancer Epidemiol Biomarkers Prev. 15:1733–1737. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Huang Q, Zu Y, Fu X and Wu T: Expression of heat shock protein 70 and 27 in non-small cell lung cancer and its clinical significance. J Huazhong Univ Sci Technolog Med Sci. 25:693–695. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Zhuang H, Jiang W, Zhang X, Qiu F, Gan Z, Cheng W, Zhang J, Guan S, Tang B, Huang Q, et al: Suppression of HSP70 expression sensitizes NSCLC cell lines to TRAIL-induced apoptosis by upregulating DR4 and DR5 and downregulating c-FLIP-L expressions. J Mol Med (Berl). 91:219–235. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Leu JI, Pimkina J, Frank A, Murphy ME and George DL: A small molecule inhibitor of inducible heat shock protein 70. Mol Cell. 36:15–27. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Leu JI, Pimkina J, Pandey P, Murphy ME and George DL: HSP70 inhibition by the small-molecule 2-phenylethynesulfonamide impairs protein clearance pathways in tumor cells. Mol Cancer Res. 9:936–947. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Granato M, Lacconi V, Peddis M, Lotti LV, Di Renzo L, Gonnella R, Santarelli R, Trivedi P, Frati L, D'Orazi G, et al: HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma. Cell Death Dis. 4:e7302013. View Article : Google Scholar : PubMed/NCBI

13 

Ma L, Sato F, Sato R, Matsubara T, Hirai K, Yamasaki M, Shin T, Shimada T, Nomura T, Mori K, et al: Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer. Oncol Rep. 31:2482–2492. 2014.PubMed/NCBI

14 

Kaiser M, Kühnl A, Reins J, Fischer S, Ortiz-Tanchez J, Schlee C, Mochmann LH, Heesch S, Benlasfer O, Hofmann WK, et al: Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia. Blood Cancer J. 1:e282011. View Article : Google Scholar : PubMed/NCBI

15 

Sekihara K, Harashima N, Tongu M, Tamaki Y, Uchida N, Inomata T and Harada M: Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells. PLoS One. 8:e787722013. View Article : Google Scholar : PubMed/NCBI

16 

Choi ES, Nam JS, Jung JY, Cho NP and Cho SD: Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer. Sci Rep. 4:71622014. View Article : Google Scholar : PubMed/NCBI

17 

Hers I, Vincent EE and Tavaré JM: Akt signalling in health and disease. Cell Signal. 23:1515–1527. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Tang JM, He QY, Guo RX and Chang XJ: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 51:181–191. 2006. View Article : Google Scholar : PubMed/NCBI

20 

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, et al: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 1773:1263–1284. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, et al: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 5:157–163. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH and Walczak H: FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity. 12:599–609. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Chan KC, Ting CM, Chan PS, Lo MC, Lo KW, Curry JE, Smyth T, Lee AW, Ng WT, Tsao GS, et al: A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation. Mol Cancer. 12:1282013. View Article : Google Scholar : PubMed/NCBI

25 

Chen W, Sin SH, Wen KW, Damania B and Dittmer DP: Hsp90 inhibitors are efficacious against Kaposi sarcoma by enhancing the degradation of the essential viral gene LANA, of the viral co-receptor EphA2 as well as other client proteins. PLoS Pathog. 8:e10030482012. View Article : Google Scholar : PubMed/NCBI

26 

Wang J, Li Z, Lin Z, Zhao B, Wang Y, Peng R, Wang M, Lu C, Shi G and Shen Y: 17-DMCHAG, a new geldanamycin derivative, inhibits prostate cancer cells through Hsp90 inhibition and survivin downregulation. Cancer Lett. 362:83–96. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Baek SH, Ko JH, Lee JH, Kim C, Lee H, Nam D, Lee J, Lee SG, Yang WM, Um JY, et al: Ginkgolic acid inhibits invasion and migration and TGF-β-induced EMT of lung cancer cells through PI3K/Akt/mTOR inactivation. J Cell Physiol. 232:346–354. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Monma H, Harashima N, Inao T, Okano S, Tajima Y and Harada M: The HSP70 and autophagy inhibitor pifithrin-μ enhances the antitumor effects of TRAIL on human pancreatic cancer. Mol Cancer Ther. 12:341–351. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Ding X, Zhang B, Pei Q, Pan J, Huang S, Yang Y, Zhu Z, Lv Y and Zou X: Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1. BMC Cancer. 14:2712014. View Article : Google Scholar : PubMed/NCBI

30 

Meng G, Wang W, Chai K, Yang S, Li F and Jiang K: Combination treatment with triptolide and hydroxycamptothecin synergistically enhances apoptosis in A549 lung adenocarcinoma cells through PP2A-regulated ERK, p38 MAPKs and Akt signaling pathways. Int J Oncol. 46:1007–1017. 2015.PubMed/NCBI

31 

Zorzi E and Bonvini P: Inducible hsp70 in the regulation of cancer cell survival: Analysis of chaperone induction, expression and activity. Cancers (Basel). 3:3921–3956. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Lee SH, Lee EJ, Min KH, Hur GY, Lee SH, Lee SY, Kim JH, Shin C, Shim JJ, In KH, et al: Quercetin enhances chemosensitivity to gemcitabine in lung cancer cells by inhibiting heat shock protein 70 expression. Clin Lung Cancer. 16:e235–e243. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Ma J, Zhang J, He L, Gong J and Long C: Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70. Oncol Rep 37: 313-322, 2017.
APA
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., & Long, C. (2017). Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70. Oncology Reports, 37, 313-322. https://doi.org/10.3892/or.2016.5286
MLA
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., Long, C."Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70". Oncology Reports 37.1 (2017): 313-322.
Chicago
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., Long, C."Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70". Oncology Reports 37, no. 1 (2017): 313-322. https://doi.org/10.3892/or.2016.5286
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Y, Ma J, Zhang J, He L, Gong J and Long C: Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70. Oncol Rep 37: 313-322, 2017.
APA
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., & Long, C. (2017). Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70. Oncology Reports, 37, 313-322. https://doi.org/10.3892/or.2016.5286
MLA
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., Long, C."Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70". Oncology Reports 37.1 (2017): 313-322.
Chicago
Zhou, Y., Ma, J., Zhang, J., He, L., Gong, J., Long, C."Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70". Oncology Reports 37, no. 1 (2017): 313-322. https://doi.org/10.3892/or.2016.5286
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