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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
December-2016 Volume 12 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
December-2016 Volume 12 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 Open Access

Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells

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

    Affiliations: Institute of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China, The Second School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730030, P.R. China
    Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4577-4583
    |
    Published online on: October 13, 2016
       https://doi.org/10.3892/ol.2016.5255
  • 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

It has been well-established that apoptosis contributes to cancer cell death; however, the role of autophagy in cancer cell death remains unclear. The aim of the present study was to investigate the effects of rottlerin, a traditional Indian medicine, on cell growth inhibition and autophagy in EJ human bladder carcinoma cells in vitro. Cell viability, measured by MTT assay, was found to be suppressed in a dose‑ and time‑dependent manner. In addition, apoptosis was significantly increased in cells treated with rottlerin, as indicated by increased annexin V-fluorescein isothiocyanate/propidium iodide staining and changes in the cell cycle distribution that indicated blockage at G1 phase. Rottlerin treatment also enhanced the activation of autophagy, with increased expression of microtubule-associated protein 1 light chain 3 (LC3)‑II and the appearance of autophagosomes. The increased level of LC3‑II and autophagosomes suggests that autophagy may contribute to apoptosis in these cells. In addition, no apparent alterations in the levels of pro‑caspase‑3, cleaved caspase‑3, total poly (ADP ribose) polymerase (PARP) and cleaved‑PARP were observed in cells treated with rottlerin, which indicates that caspases may not serve a key role during the process of apoptosis induced by rottlerin. Therefore, the results of the present study indicate that rottlerin promotes apoptosis and arrests the cell cycle in EJ cells, which may be caused by autophagy activation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Vishnu P, Mathew J and Tan WW: Current therapeutic strategies for invasive and metastatic bladder cancer. Onco Targets Ther. 4:97–113. 2011.PubMed/NCBI

3 

Shariat SF, Karam JA, Lotan Y and Karakiewizc PI: Critical evaluation of urinary markers for bladder cancer detection and monitoring. Rev Urol. 10:120–135. 2008.PubMed/NCBI

4 

Bellmunt J, Orsola A, Wiegel T, Guix M, De Santis M and Kataja V: ESMO Guidelines Working Group: Bladder cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 22:(Suppl 6). Svi45–Svi49. 2011. View Article : Google Scholar

5 

Tanaka T, Miyazawa K, Tsukamoto T, Kuno T and Suzuki K: Pathobiology and chemoprevention of bladder cancer. J Oncol. 2011:5283532011. View Article : Google Scholar : PubMed/NCBI

6 

Gschwendt M, Müller HJ, Kielbassa K, Zang R, Kittstein W, Rincke G and Marks F: Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun. 199:93–98. 1994. View Article : Google Scholar : PubMed/NCBI

7 

Liao YF, Hung YC, Chang WH, Tsay GJ, Hour TC, Hung HC and Liu GY: The PKC delta inhibitor, rottlerin, induces apoptosis of haematopoietic cell lines through mitochondrial membrane depolarization and caspases' cascade. Life Sci. 77:707–719. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Ni H, Ergin M, Tibudan SS, Denning MF, Izban KF and Alkan S: Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis. Br J Haematol. 121:849–856. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Valacchi G, Pecorelli A, Sticozzi C, Torricelli C, Muscettola M, Aldinucci C and Maioli E: Rottlerin exhibits antiangiogenic effects in vitro. Chem Biol Drug Des. 77:460–470. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Maioli E, Greci L, Soucek K, Hyzdalova M, Pecorelli A, Fortino V and Valacchi G: Rottlerin inhibits ROS formation and prevents NF kappaB activation in MCF-7 and HT-29 cells. J Biomed Biotechnol. 2009:7429362009. View Article : Google Scholar : PubMed/NCBI

11 

Mizushima N and Klionsky DJ: Protein turnover via autophagy: Implications for metabolism. Annu Rev Nutr. 27:19–40. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Doria A, Gatto M and Punzi L: Autophagy in human health and disease. N Engl J Med. 368:18452013. View Article : Google Scholar : PubMed/NCBI

13 

Hippert MM, O'Toole PS and Thorburn A: Autophagy in cancer: Good, bad, or both? Cancer Res. 66:9349–9351. 2006. View Article : Google Scholar : PubMed/NCBI

14 

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

15 

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

16 

Wang YX, Xu SQ, Chen XH, Liu RS and Liang ZQ: Autophagy involvement in olanzapine-mediated cytotoxic effects in human glioma cells. Asian Pac J Cancer Prev. 15:8107–8113. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Deretic V, Delgado M, Vergne I, Master S, De Haro S, Ponpuak M and Singh S: Autophagy in Immunity against mycobacterium tuberculosis: A model system to dissect immunological roles of autophagy. Curr Top Microbiol Immunol. 335:169–188. 2009.PubMed/NCBI

18 

Singh BN, Kumar D, Shankar S and Srivastava RK: Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol. 84:1154–1163. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Zhivotovsky B, Samali A, Gahm A and Orrenius S: Caspases: Their intracellular localization and translocation during apoptosis. Cell Death Differ. 6:644–651. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Lu QY, Zhang L, Lugea A, Moro A, Edderkaoui M, Eibl G, Pandol SJ and Go VL: Determination of rottlerin, a natural protein kinases C inhibitor, in pancreatic cancer cells and mouse xenografts by RP-HPLC method. J Chromatogr Sep Tech. 4(pii): 1000622013.PubMed/NCBI

21 

Gangwar M, Goel RK and Nath G: Mallotus philippinensis Muell. Arg (Euphorbiaceae): Ethnopharmacology and phytochemistry review. Biomed Res Int. 2014:2139732014. View Article : Google Scholar : PubMed/NCBI

22 

Kumar VP, Chauhan NS, Padh H and Rajani M: Search for antibacterial and antifungal agents from selected Indian medicinal plants. J Ethnopharmacol. 107:182–188. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Arfan M, Hazrat K, Magdalena K, Kosińka A, Wiczkowski W and Amarowicz R: Antioxidant activity of phenolic fractions of Mallotus philippinensis bark extract. J Food Sci. 27:109–117. 2009.

24 

Tiwari AK: Imbalance in antioxidant defence and human diseases: Multiple approach of natural antioxidants therapy. Current Science. 81:1179–1187. 2001.

25 

Gangwar M, Gautam MK, Sharma AK, Tripathi YB, Goel RK and Nath G: Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: An in vitro study. Scientific World Journal. 2014:2794512014. View Article : Google Scholar : PubMed/NCBI

26 

Li X, Li X, Wang J, Ye Z and Li JC: Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int J Biol Sci. 8:901–912. 2012. View Article : Google Scholar : PubMed/NCBI

27 

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

28 

Chen YS, Song HX, Lu Y, Li X, Chen T, Zhang Y, Xue JX, Liu H, Kan B, Yang G and Fu T: Autophagy inhibition contributes to radiation sensitization of esophageal squamous carcinoma cells. Dis Esophagus. 24:437–443. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Liu DL, Gao M, Yang Y, Qi Y, Wu K and Zhao S: Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells. Oncol Lett. 9:2278–2282. 2015.PubMed/NCBI

30 

Choi S, Lim MH, Kim KM, Jeon BH, Song WO and Kim TW: Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor. Toxicol Appl Pharmacol. 257:165–173. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Li Y, Li R, Zhu S, Zhou R, Wang L, Du J, Wang Y, Zhou B and Mai L: Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells. Oncol Lett. 9:2541–2547. 2015.PubMed/NCBI

32 

He Z, Mangala LS, Theriot CA, Rohde LH and Wu and Zhang Y: Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. J Radiat Res. 53:225–233. 2012. View Article : Google Scholar : PubMed/NCBI

33 

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.PubMed/NCBI

34 

Kang M, Jeong CW, Ku JH, Kwak C and Kim HH: Inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro. Int J Mol Sci. 15:8106–8121. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Ringer L, Sirajuddin P, Tricoli L, Waye S, Choudhry MU, Parasido E, Sivakumar A, Heckler M, Naeem A, Abdelgawad I, et al: The induction of the p53 tumor suppressor protein bridges the apoptotic and autophagic signaling pathways to regulate cell death in prostate cancer cells. Oncotarget. 5:10678–10691. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Orelio C, Harvey KN, Miles C, Oostendorp RA, van der Horn K and Dzierzak E: The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression. Blood. 103:4084–4092. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Ashkenazi A and Dixit VM: Death receptors: Signaling and modulation. Science. 281:1305–1308. 1998. View Article : Google Scholar : PubMed/NCBI

38 

Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI

39 

Ron D and Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519–529. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Tabas I and Ron D: Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 13:184–190. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Bleackley RC and Heibein JA: Enzymatic control of apoptosis. Nat Prod Rep. 18:431–440. 2001. View Article : Google Scholar : PubMed/NCBI

42 

Song KS, Kim JS, Yun EJ, Kim YR, Seo KS, Park JH, Jung YJ, Park JI, Kweon GR, Yoon WH, et al: Rottlerin induces autophagy and apoptotic cell death through a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells: The protective role of autophagy in apoptosis. Autophagy. 4:650–658. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Kumar D, Shankar S and Srivastava RK: Rottlerin-induced autophagy leads to the apoptosis in breast cancer stem cells: Molecular mechanisms. Mol Cancer. 12:1712013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qi P, He Z, Zhang L, Fan Y and Wang Z: Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells. Oncol Lett 12: 4577-4583, 2016.
APA
Qi, P., He, Z., Zhang, L., Fan, Y., & Wang, Z. (2016). Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells. Oncology Letters, 12, 4577-4583. https://doi.org/10.3892/ol.2016.5255
MLA
Qi, P., He, Z., Zhang, L., Fan, Y., Wang, Z."Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells". Oncology Letters 12.6 (2016): 4577-4583.
Chicago
Qi, P., He, Z., Zhang, L., Fan, Y., Wang, Z."Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells". Oncology Letters 12, no. 6 (2016): 4577-4583. https://doi.org/10.3892/ol.2016.5255
Copy and paste a formatted citation
x
Spandidos Publications style
Qi P, He Z, Zhang L, Fan Y and Wang Z: Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells. Oncol Lett 12: 4577-4583, 2016.
APA
Qi, P., He, Z., Zhang, L., Fan, Y., & Wang, Z. (2016). Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells. Oncology Letters, 12, 4577-4583. https://doi.org/10.3892/ol.2016.5255
MLA
Qi, P., He, Z., Zhang, L., Fan, Y., Wang, Z."Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells". Oncology Letters 12.6 (2016): 4577-4583.
Chicago
Qi, P., He, Z., Zhang, L., Fan, Y., Wang, Z."Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells". Oncology Letters 12, no. 6 (2016): 4577-4583. https://doi.org/10.3892/ol.2016.5255
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