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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2015 Volume 11 Issue 6

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
June-2015 Volume 11 Issue 6

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

Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

  • Authors:
    • Zhenhua He
    • Jingmin Yuan
    • Ping Qi
    • Lixiu Zhang
    • Zhiping Wang
  • View Affiliations / Copyright

    Affiliations: School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Pain, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Institute of Urology and Key Laboratory of Urological Diseases in Gansu, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
  • Pages: 4403-4408
    |
    Published online on: February 11, 2015
       https://doi.org/10.3892/mmr.2015.3334
  • 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

Athough it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy‑associated gene expression profile in the PC3 prostate carcinoma cell line. The atorvastatin‑induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)‑II, using immunoblotting and counting of green fluorescent protein (GFP)‑LC3-transfected autophagic cells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Atorvastatin treatment of PC3 cells for 24 h increased the expression of green fluorescent protein‑LC3‑II by >25%, and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, DeSantis C, Virgo K, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Sun F, Oyesanmi O, Fontanarosa J, Reston J, Guzzo T and Schoelles K: Therapies for clinically localized prostate cancer: Update of a 2008 systematic review. AHRQ Comparative Effectiveness Reviews: 15-EHC004-EF. 2014

4 

Dozmorov MG, Hurst RE, Culkin DJ, et al: Unique patterns of molecular profiling between human prostate cancer LNCaP and PC-3 cells. Prostate. 69:1077–1090. 2009. View Article : Google Scholar : PubMed/NCBI

5 

An J, Chervin AS, Nie A, Ducoff HS and Huang Z: Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene. 26:652–661. 2007. View Article : Google Scholar

6 

Marcelli M, Marani M, Li X, et al: Heterogeneous apoptotic responses of prostate cancer cell lines identify an association between sensitivity to staurosporine-induced apoptosis, expression of Bcl-2 family members and caspase activation. Prostate. 42:260–273. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R and Collins R; Prospective Studies Collaboration: Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 370:1829–1839. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Sassano A and Platanias LC: Statins in tumor suppression. Cancer Lett. 260:11–19. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Chan KK, Oza AM and Siu LL: The statins as anticancer agents. Clin Cancer Res. 9:10–19. 2003.PubMed/NCBI

10 

Parikh A, Childress C, Deitrick K, Lin Q, Rukstalis D and Yang W: Statin-induced autophagy by inhibition of geranylgeranyl biosynthesis in prostate cancer PC3 cells. Prostate. 70:971–981. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Schleicher SM, Moretti L, Varki V and Lu B: Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: implications for future therapeutic approaches. Drug Resist Updat. 13:79–86. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Park WH, Kim ES, Kim BK and Lee YY: Monensin-mediated growth inhibition in NCI-H929 myeloma cells via cell cycle arrest and apoptosis. Int J Oncol. 23:197–204. 2003.PubMed/NCBI

13 

Robinson SM, Tsueng G, Sin J, et al: Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers. PLoS Pathog. 10:e10040452014. View Article : Google Scholar : PubMed/NCBI

14 

Gong JS and Kim GJ: The role of autophagy in the placenta as a regulator of cell death. Clin Exp Reprod Med. 41:97–107. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Hannigan AM and Gorski SM: Macroautophagy: the key ingredient to a healthy diet? Autophagy. 5:140–151. 2009. View Article : Google Scholar

16 

Nishino I: Autophagic vacuolar myopathy. Semin Pediatr Neurol. 13:90–95. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Gozuacik D and Kimchi A: Autophagy and cell death. Curr Top Dev Biol. 78:217–245. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Yang ZJ, Chee CE, Huang S and Sinicrope F: Autophagy modulation for cancer therapy. Cancer Biol Ther. 11:169–176. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Yue Z, Jin S, Yang C, Levine AJ and Heintz N: Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 100:15077–15082. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Park MA, Zhang G, Martin AP, et al: Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol Ther. 7:1648–1662. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Katayama M, Kawaguchi T, Berger MS and Pieper RO: DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ. 14:548–558. 2007. View Article : Google Scholar

22 

Cao C, Subhawong T, Albert JM, et al: Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res. 66:10040–10047. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Duffy A, Le J, Sausville E and Emadi A: Autophagy modulation: a target for cancer treatment development. Cancer Chemother Pharmacol. Nov 25–2014.Epub ahead of print. PubMed/NCBI

24 

Song X, Liu H, Wang X, Li Z and Huang C: Atorvastatin combined with poly-unsaturated fatty acid confers better improvement of dyslipidemia and endothelium function. Lipids Health Dis. 13:1862014. View Article : Google Scholar : PubMed/NCBI

25 

Pearson T, Ballantyne C, Sisk C, Shah A, Veltri E and Maccubbin D: Comparison of effects of ezetimibe/simvastatin versus simvastatin versus atorvastatin in reducing C-reactive protein and low-density lipoprotein cholesterol levels. Am J Cardiol. 99:1706–1713. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Yang PM, Liu YL, Lin YC, Shun CT, Wu MS and Chen CC: Inhibition of autophagy enhances anticancer effects of atorvastatin in digestive malignancies. Cancer Res. 70:7699–7709. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Heymann D: Autophagy: A protective mechanism in response to stress and inflammation. Curr Opin Investig Drugs. 7:443–450. 2006.PubMed/NCBI

28 

He Z, Zhang Y, Mehta SK, Pierson DL, Wu H and Rohde LH: Expression profile of apoptosis related genes and radio-sensitivity of prostate cancer cells. J Radiat Res. 52:743–751. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Zhu K, Dunner K Jr and McConkey DJ: Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene. 29:451–462. 2010. View Article : Google Scholar :

30 

Umemiya-Shirafuji R, Matsuo T, Liao M, Boldbaatar D, Battur B, Suzuki H and Fujisaki K: Increased expression of ATG genes during nonfeeding periods in the tick Haemaphysalis longicornis. Autophagy. 6:473–481. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Aguilera MO, Berón W and Colombo MI: The actin cytoskeleton participates in the early events of autophagosome formation upon starvation induced autophagy. Autophagy. 8:1590–1603. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Levine B: Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell. 120:159–162. 2005.PubMed/NCBI

33 

Yu C, Wang L, Lv B, et al: TMEM74, a lysosome and autophagosome protein, regulates autophagy. Biochem Biophys Res Commun. 369:622–629. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Kirkin V, McEwan DG, Novak I and Dikic I: A role for ubiquitin in selective autophagy. Mol Cell. 34:259–269. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Behrends C, Sowa ME, Gygi SP and Harper JW: Network organization of the human autophagy system. Nature. 466:68–76. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Levine B and Yuan J: Autophagy in cell death: an innocent convict? J Clin Invest. 115:2679–2688. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Berry DL and Baehrecke EH: Autophagy functions in programmed cell death. Autophagy. 4:359–360. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB and Tsujimoto Y: Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 6:1221–1228. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Espert L, Denizot M, Grimaldi M, et al: Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest. 116:2161–2172. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Chen ZH, Lam HC, Jin Y, et al: Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci USA. 107:18880–18885. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Weber JD, Jeffers JR, Rehg JE, et al: p53-independent functions of the p19(ARF) tumor suppressor. Genes Dev. 14:2358–2365. 2000. View Article : Google Scholar : PubMed/NCBI

42 

Matsuoka M, Kurita M, Sudo H, Mizumoto K, Nishimoto I and Ogata E: Multiple domains of the mouse p19ARF tumor suppressor are involved in p53-independent apoptosis. Biochem Biophys Res Commun. 301:1000–1010. 2003. View Article : Google Scholar : PubMed/NCBI

43 

Paliwal S, Pande S, Kovi RC, Sharpless NE, Bardeesy N and Grossman SR: Targeting of C-terminal binding protein (CtBP) by ARF results in p53-independent apoptosis. Mol Cell Biol. 26:2360–2372. 2006. View Article : Google Scholar : PubMed/NCBI

44 

Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H and Levine B: Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 402:672–676. 1999. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
He Z, Yuan J, Qi P, Zhang L and Wang Z: Atorvastatin induces autophagic cell death in prostate cancer cells in vitro. Mol Med Rep 11: 4403-4408, 2015.
APA
He, Z., Yuan, J., Qi, P., Zhang, L., & Wang, Z. (2015). Atorvastatin induces autophagic cell death in prostate cancer cells in vitro. Molecular Medicine Reports, 11, 4403-4408. https://doi.org/10.3892/mmr.2015.3334
MLA
He, Z., Yuan, J., Qi, P., Zhang, L., Wang, Z."Atorvastatin induces autophagic cell death in prostate cancer cells in vitro". Molecular Medicine Reports 11.6 (2015): 4403-4408.
Chicago
He, Z., Yuan, J., Qi, P., Zhang, L., Wang, Z."Atorvastatin induces autophagic cell death in prostate cancer cells in vitro". Molecular Medicine Reports 11, no. 6 (2015): 4403-4408. https://doi.org/10.3892/mmr.2015.3334
Copy and paste a formatted citation
x
Spandidos Publications style
He Z, Yuan J, Qi P, Zhang L and Wang Z: Atorvastatin induces autophagic cell death in prostate cancer cells in vitro. Mol Med Rep 11: 4403-4408, 2015.
APA
He, Z., Yuan, J., Qi, P., Zhang, L., & Wang, Z. (2015). Atorvastatin induces autophagic cell death in prostate cancer cells in vitro. Molecular Medicine Reports, 11, 4403-4408. https://doi.org/10.3892/mmr.2015.3334
MLA
He, Z., Yuan, J., Qi, P., Zhang, L., Wang, Z."Atorvastatin induces autophagic cell death in prostate cancer cells in vitro". Molecular Medicine Reports 11.6 (2015): 4403-4408.
Chicago
He, Z., Yuan, J., Qi, P., Zhang, L., Wang, Z."Atorvastatin induces autophagic cell death in prostate cancer cells in vitro". Molecular Medicine Reports 11, no. 6 (2015): 4403-4408. https://doi.org/10.3892/mmr.2015.3334
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