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
October 2012 Volume 41 Issue 4

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
October 2012 Volume 41 Issue 4

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

Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis

  • Authors:
    • Se-Lim Kim
    • Kieu The Thu Trang
    • Seong Hun Kim
    • In Hee Kim
    • Seung Ok Lee
    • Soo Teik Lee
    • Dae Ghon Kim
    • Sang-Wook Kim
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine and Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju 561-712, Republic of Korea
  • Pages: 1547-1553
    |
    Published online on: August 9, 2012
       https://doi.org/10.3892/ijo.2012.1587
  • 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

Parthenolide (PT), a principal active component in medicinal plants, has been used conventionally to treat migraine and inflammation. This component has recently been reported to induce apoptosis in cancer cells, through mitochondrial dysfunction. In the present study, we investigated PT-mediated cell death signaling pathway by focusing on the involvement of Bcl-2 family members in human colorectal cancer cells. We also investigated the inhibitory effect of PT on tumor growth in xenografts. Using the human colorectal cancer cell lines HT-29, SW620 and LS174T, we demonstrated that treatment of these cancer cells with PT induces apoptosis using MTT, Annexin V assay and Hoechst 33258 staining. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, cytochrome c release and caspase activation. Moreover, intraperitoneal injection of PT showed significant inhibition of tumor growth, angiogenesis in the xenograft model. These results demonstrate that PT exhibits anti-cancer activity in human colorectal cancer in vitro and in vivo. These findings may also provide a novel approach for the treatment of colorectal cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar

2 

Meyerhardt JA and Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med. 352:476–487. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Tebbutt NC, Cattell E, Midgley R, Cunningham D and Kerr D: Systemic treatment of colorectal cancer. Eur J Cancer. 38:1000–1015. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Gusella M, Frigo AC, Bolzonella C, et al: Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. Br J Cancer. 100:1549–1557. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Raymond E, Faivre S, Chaney S, Woynarowski J and Cvitkovic E: Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 1:227–235. 2002.

6 

Knight DW: Feverfew: chemistry and biological activity. Nat Prod Rep. 12:271–276. 1995. View Article : Google Scholar : PubMed/NCBI

7 

Murphy JJ, Heptinstall S and Mitchell JR: Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet. 2:189–192. 1988. View Article : Google Scholar : PubMed/NCBI

8 

Hehner SP, Heinrich M, Bork PM, et al: Sesquiterpene lactones specifically inhibit activation of NF-kappa B by preventing the degradation of I kappa B-alpha and I kappa B-beta. J Biol Chem. 273:1288–1297. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Lyss G, Knorre A, Schmidt TJ, Pahl HL and Merfort I: The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65. J Biol Chem. 273:33508–33516. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Zhang S, Ong CN and Shen HM: Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett. 208:143–153. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Wen J, You KR, Lee SY, Song CH and Kim DG: Oxidative stress-mediated apoptosis. The anticancer effect of the sesquiterpene lactone parthenolide J Biol Chem. 277:38954–38964. 2002.PubMed/NCBI

12 

Pajak B, Gajkowska B and Orzechowski A: Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells. Folia Histochem Cytobiol. 46:129–135. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Mathema VB, Koh YS, Thakuri BC and Sillanpaa M: Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation. 35:560–565. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Zhao LJ, Xu YH and Li Y: Effect of parthenolide on proliferation and apoptosis in gastric cancer cell line SGC7901. J Dig Dis. 10:172–180. 2009. View Article : Google Scholar

15 

Zhang S, Ong CN and Shen HM: Involvement of proapoptotic Bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis. Cancer Lett. 211:175–188. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Chen YC, Shen SC, Lee WR, et al: Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol. 64:1713–1724. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Grutter MG: Caspases: key players in programmed cell death. Curr Opin Struct Biol. 10:649–655. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Yang JC and Cortopassi GA: Induction of the mitochondrial permeability transition causes release of the apoptogenic factor cytochrome c. Free Radic Biol Med. 24:624–631. 1998. View Article : Google Scholar : PubMed/NCBI

19 

Tacchini L, De Ponti C, Matteucci E, Follis R and Desiderio MA: Hepatocyte growth factor-activated NF-kappaB regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines. Carcinogenesis. 25:2089–2100. 2004. View Article : Google Scholar

20 

Dai Y, Guzman ML, Chen S, et al: The NF (nuclear factor)-kappaB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells. Br J Haematol. 151:70–83. 2010. View Article : Google Scholar

21 

Nakshatri H, Rice SE and Bhat-Nakshatri P: Antitumor agent parthenolide reverses resistance of breast cancer cells to tumor necrosis factor-related apoptosis-inducing ligand through sustained activation of c-Jun N-terminal kinase. Oncogene. 23:7330–7344. 2004. View Article : Google Scholar

22 

Carlisi D, D’Anneo A, Angileri L, et al: Parthenolide sensitizes hepatocellular carcinoma cells to TRAIL by inducing the expression of death receptors through inhibition of STAT3 activation. J Cell Physiol. 226:1632–1641. 2011. View Article : Google Scholar

23 

Chen KF, Tai WT, Liu TH, et al: Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3. Clin Cancer Res. 16:5189–5199. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Wu C, Chen F, Rushing JW, et al: Antiproliferative activities of parthenolide and golden feverfew extract against three human cancer cell lines. J Med Food. 9:55–61. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Fernandes-Alnemri T, Litwack G and Alnemri ES: CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 269:30761–30764. 1994.PubMed/NCBI

26 

Mehmet H: Caspases find a new place to hide. Nature. 403:29–30. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Yang E and Korsmeyer SJ: Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood. 88:386–401. 1996.PubMed/NCBI

28 

Green DR and Reed JC: Mitochondria and apoptosis. Science. 281:1309–1312. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Reed JC: Double identity for proteins of the Bcl-2 family. Nature. 387:773–776. 1997. 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 

Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Terrones O, Antonsson B, Yamaguchi H, et al: Lipidic pore formation by the concerted action of proapoptotic BAX and tBID. J Biol Chem. 279:30081–30091. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Van Mau N, Kajava AV, Bonfils C, Martinou JC and Harricane MC: Interactions of Bax and tBid with lipid monolayers. J Membr Biol. 207:1–9. 2005.PubMed/NCBI

34 

Coutts AS and La Thangue N: The p53 response during DNA damage: impact of transcriptional cofactors. Biochem Soc Symp. 181–189. 2006.PubMed/NCBI

35 

Kroemer G and Reed JC: Mitochondrial control of cell death. Nat Med. 6:513–519. 2000. View Article : Google Scholar

36 

Borner C: The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 39:615–647. 2003. View Article : Google Scholar : PubMed/NCBI

37 

Ferrara N, Hillan KJ, Gerber HP and Novotny W: Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 3:391–400. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Huang S, Pettaway CA, Uehara H, Bucana CD and Fidler IJ: Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene. 20:4188–4197. 2001. View Article : Google Scholar : PubMed/NCBI

39 

Oka D, Nishimura K, Shiba M, et al: Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-kappaB. Int J Cancer. 120:2576–2581. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Weng SX, Sui MH, Chen S, et al: Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest. J Zhejiang Univ Sci B. 10:528–535. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim S, Trang KT, Kim SH, Kim IH, Lee SO, Lee ST, Kim DG and Kim S: Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis. Int J Oncol 41: 1547-1553, 2012.
APA
Kim, S., Trang, K.T., Kim, S.H., Kim, I.H., Lee, S.O., Lee, S.T. ... Kim, S. (2012). Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis. International Journal of Oncology, 41, 1547-1553. https://doi.org/10.3892/ijo.2012.1587
MLA
Kim, S., Trang, K. T., Kim, S. H., Kim, I. H., Lee, S. O., Lee, S. T., Kim, D. G., Kim, S."Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis". International Journal of Oncology 41.4 (2012): 1547-1553.
Chicago
Kim, S., Trang, K. T., Kim, S. H., Kim, I. H., Lee, S. O., Lee, S. T., Kim, D. G., Kim, S."Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis". International Journal of Oncology 41, no. 4 (2012): 1547-1553. https://doi.org/10.3892/ijo.2012.1587
Copy and paste a formatted citation
x
Spandidos Publications style
Kim S, Trang KT, Kim SH, Kim IH, Lee SO, Lee ST, Kim DG and Kim S: Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis. Int J Oncol 41: 1547-1553, 2012.
APA
Kim, S., Trang, K.T., Kim, S.H., Kim, I.H., Lee, S.O., Lee, S.T. ... Kim, S. (2012). Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis. International Journal of Oncology, 41, 1547-1553. https://doi.org/10.3892/ijo.2012.1587
MLA
Kim, S., Trang, K. T., Kim, S. H., Kim, I. H., Lee, S. O., Lee, S. T., Kim, D. G., Kim, S."Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis". International Journal of Oncology 41.4 (2012): 1547-1553.
Chicago
Kim, S., Trang, K. T., Kim, S. H., Kim, I. H., Lee, S. O., Lee, S. T., Kim, D. G., Kim, S."Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis". International Journal of Oncology 41, no. 4 (2012): 1547-1553. https://doi.org/10.3892/ijo.2012.1587
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