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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
September 2012 Volume 41 Issue 3

Full Size Image

Cover Legend PDF

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
September 2012 Volume 41 Issue 3

Full Size Image

Cover Legend PDF

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

Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells

  • Authors:
    • Chien-Chih Yu
    • Fang-Yu Ko
    • Chun-Shu Yu
    • Chin-Chung Lin
    • Yi‑Ping  Huang
    • Jai-Sing Yang
    • Jing-Pin Lin
    • Jing-Gung Chung
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Cosmeceutics, China Medical University, Taichung, Taiwan, R.O.C., Department of Chinese Medicine, Fong-Yuan Hospital, Department of Health, Executive Yuan, Taichung 420, Taiwan, R.O.C., Department of Physiology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C., School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
  • Pages: 1050-1060
    |
    Published online on: June 7, 2012
       https://doi.org/10.3892/ijo.2012.1511
  • 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

Norcantharidin (NCTD) is one of the ingredients of blister beetles which have been used in Chinese medicine for a long time. The purpose of this study was to investigate the inhibitory effects of NCTD on TSGH 8301 human bladder cancer cells in vitro and the mechanisms through which it exerts its anticancer action. Cell morphological analysis was performed using a phase-contrast microscope. The percentage of viable cells, cell cycle distribution, sub-G1 phase (apoptosis), reactive oxygen species (ROS) production and the levels of mitochondrial membrane potential (∆Ψm) were analyzed by flow cytometry. DNA condensation and damage were determined by DAPI staining and comet assay. Apoptosis-associated protein level changes in TSGH 8301 cells following exposure to NCTD were examined, measured and determined by western blotting. Analysis of protein translocation was conducted by immunostaining and confocal laser microscopy. The results indicated that NCTD promoted cytotoxic effects, including the induction of cell morphological changes and the decrease in the percentage of viability, the induction of S-phase arrest as well as sub-G1 phase (apoptosis) in TSGH 8301 cells. The activities of caspase-3 and -9 were upregulated following NCTD treatment. Western blotting indicated that NCTD upregulated Fas, FasL, Bax, Bid, cytochrome c, caspase-3, -8 and -9 that led to the induction of apoptosis through the Fas extrinsic pathway. Furthermore, NCTD induced AIF and Endo G that were released from mitochondria to induce apoptosis through the mitochondrial-independent pathway. NCTD upregulated ROS production, downregulated ∆Ψm and ERK, JNK, p38 protein kinases in TSGH 8301 cells. These findings suggest that NCTD triggers apoptosis in TSGH 8301 human bladder cancer cells via the Fas receptor, activation of the caspse-8, -9 and -3, mitochondrial-dependent and -independent pathways. NCTD may be useful for developing new therapeutic regimens for the treatment of bladder cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1. 

Chen RJ, Ho CT and Wang YJ: Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. Mol Nutr Food Res. 54:1819–1832. 2010. View Article : Google Scholar : PubMed/NCBI

2. 

Singh RP, Dhanalakshmi S and Agarwal R: Phytochemicals as cell cycle modulators - a less toxic approach in halting human cancers. Cell Cycle. 1:156–161. 2002. View Article : Google Scholar : PubMed/NCBI

3. 

Degterev A, Boyce M and Yuan J: A decade of caspases. Oncogene. 22:8543–8567. 2003. View Article : Google Scholar : PubMed/NCBI

4. 

Ziegler DS and Kung AL: Therapeutic targeting of apoptosis pathways in cancer. Curr Opin Oncol. 20:97–103. 2008. View Article : Google Scholar : PubMed/NCBI

5. 

Klein S, McCormick F and Levitzki A: Killing time for cancer cells. Nat Rev Cancer. 5:573–580. 2005. View Article : Google Scholar

6. 

Kao ST, Yeh CC, Hsieh CC, et al: The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest. Life Sci. 69:1485–1496. 2001. View Article : Google Scholar : PubMed/NCBI

7. 

Gamet-Payrastre L, Li P, Lumeau S, et al: Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 60:1426–1433. 2000.PubMed/NCBI

8. 

Wang GS: Medical uses of mylabris in ancient China and recent studies. J Ethnopharmacol. 26:147–162. 1989. View Article : Google Scholar : PubMed/NCBI

9. 

Peng F, Wei YQ, Tian L, et al: Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand. J Cancer Res Clin Oncol. 128:223–230. 2002. View Article : Google Scholar : PubMed/NCBI

10. 

Huang Y, Liu Q, Liu K, Yagasaki K and Zhang G: Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action. Cytotechnology. 59:2092009. View Article : Google Scholar

11. 

Chen YN, Chen JC, Yin SC, et al: Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells. Int J Cancer. 100:158–165. 2002. View Article : Google Scholar : PubMed/NCBI

12. 

Fan YZ, Zhao ZM, Fu JY and Chen CQ: Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo. Zhonghua Wai Ke Za Zhi. 44:618–622. 2006.(In Chinese).

13. 

Chang C, Zhu YQ, Mei JJ, Liu SQ and Luo J: Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells. J Exp Clin Cancer Res. 29:1452010. View Article : Google Scholar : PubMed/NCBI

14. 

Luan J, Duan H, Liu Q, Yagasaki K and Zhang G: Inhibitory effects of norcantharidin against human lung cancer cell growth and migration. Cytotechnology. 62:349–355. 2010. View Article : Google Scholar : PubMed/NCBI

15. 

Chen YJ, Tsai YM, Kuo CD, Ku KL, Shie HS and Liao HF: Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect. Life Sci. 85:642–651. 2009. View Article : Google Scholar : PubMed/NCBI

16. 

Kok SH, Cheng SJ, Hong CY, et al: Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio. Cancer Lett. 217:43–52. 2005. View Article : Google Scholar : PubMed/NCBI

17. 

Kok SH, Hong CY, Kuo MY, et al: Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes. Oral Oncol. 39:19–26. 2003. View Article : Google Scholar : PubMed/NCBI

18. 

Peng C, Liu X, Liu E, et al: Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6-extracellular signal-related kinase signaling pathway. Cancer Sci. 100:2302–2308. 2009. View Article : Google Scholar : PubMed/NCBI

19. 

Lu CC, Yang JS, Huang AC, et al: Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res. 54:967–976. 2010. View Article : Google Scholar : PubMed/NCBI

20. 

Chiang JH, Yang JS, Ma CY, et al: Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol. 24:20–29. 2011. View Article : Google Scholar

21. 

Kuo JH, Chu YL, Yang JS, et al: Cantharidin induces apoptosis in human bladder cancer TSGH 8301 cells through mitochondria-dependent signal pathways. Int J Oncol. 37:1243–1250. 2010.PubMed/NCBI

22. 

Saile B, Eisenbach C, El-Armouche H, Neubauer K and Ramadori G: Antiapoptotic effect of interferon-alpha on hepatic stellate cells (HSC): a novel pathway of IFN-alpha signal transduction via Janus kinase 2 (JAK2) and caspase-8. Eur J Cell Biol. 82:31–41. 2003. View Article : Google Scholar : PubMed/NCBI

23. 

Lee YJ, Song JJ, Kim JH, Kim HR and Song YK: Low extracellular pH augments TRAIL-induced apoptotic death through the mitochondria-mediated caspase signal transduction pathway. Exp Cell Res. 293:129–143. 2004. View Article : Google Scholar : PubMed/NCBI

24. 

Kikuchi T, Akazawa H, Tabata K, et al: 3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line. Chem Pharm Bull (Tokyo). 59:378–381. 2011. View Article : Google Scholar : PubMed/NCBI

25. 

Glick RD, Swendeman SL, Coffey DC, et al: Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma. Cancer Res. 59:4392–4399. 1999.PubMed/NCBI

26. 

Boldin MP, Goncharov TM, Goltsev YV and Wallach D: Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 85:803–815. 1996. View Article : Google Scholar : PubMed/NCBI

27. 

Liu KC, Huang YT, Wu PP, et al: The roles of AIF and Endo G in the apoptotic effects of benzyl isothiocyanate on DU 145 human prostate cancer cells via the mitochondrial signaling pathway. Int J Oncol. 38:787–796. 2011.PubMed/NCBI

28. 

Huan SK, Lee HH, Liu DZ, Wu CC and Wang CC: Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line. Toxicology. 223:136–143. 2006. View Article : Google Scholar : PubMed/NCBI

29. 

Rauh R, Kahl S, Boechzelt H, Bauer R, Kaina B and Efferth T: Molecular biology of cantharidin in cancer cells. Chin Med. 2:82007. View Article : Google Scholar : PubMed/NCBI

30. 

Adams JM and Cory S: The Bcl-2 protein family: arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI

31. 

Zhang R, Humphreys I, Sahu RP, Shi Y and Srivastava SK: In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis. 13:1465–1478. 2008. View Article : Google Scholar : PubMed/NCBI

32. 

Ott M, Gogvadze V, Orrenius S and Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis. 12:913–922. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yu C, Ko F, Yu C, Lin C, Huang YP, Yang J, Lin J and Chung J: Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells . Int J Oncol 41: 1050-1060, 2012.
APA
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J. ... Chung, J. (2012). Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells . International Journal of Oncology, 41, 1050-1060. https://doi.org/10.3892/ijo.2012.1511
MLA
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J., Lin, J., Chung, J."Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells ". International Journal of Oncology 41.3 (2012): 1050-1060.
Chicago
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J., Lin, J., Chung, J."Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells ". International Journal of Oncology 41, no. 3 (2012): 1050-1060. https://doi.org/10.3892/ijo.2012.1511
Copy and paste a formatted citation
x
Spandidos Publications style
Yu C, Ko F, Yu C, Lin C, Huang YP, Yang J, Lin J and Chung J: Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells . Int J Oncol 41: 1050-1060, 2012.
APA
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J. ... Chung, J. (2012). Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells . International Journal of Oncology, 41, 1050-1060. https://doi.org/10.3892/ijo.2012.1511
MLA
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J., Lin, J., Chung, J."Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells ". International Journal of Oncology 41.3 (2012): 1050-1060.
Chicago
Yu, C., Ko, F., Yu, C., Lin, C., Huang, Y., Yang, J., Lin, J., Chung, J."Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells ". International Journal of Oncology 41, no. 3 (2012): 1050-1060. https://doi.org/10.3892/ijo.2012.1511
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