Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October 2012 Volume 28 Issue 4

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
October 2012 Volume 28 Issue 4

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

Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells

  • Authors:
    • Jianteng Wei
    • Haizhou Liu
    • Ming Liu
    • Ning Wu
    • Jin Zhao
    • Lin Xiao
    • Lijun Han
    • Edward Chu
    • Xiukun Lin
  • View Affiliations / Copyright

    Affiliations: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, P.R. China, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA
  • Pages: 1339-1345
    |
    Published online on: July 19, 2012
       https://doi.org/10.3892/or.2012.1921
  • 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

The antitumor activity of oleanolic (OA) has attracted attention due to its marked antitumor effects and pharmacological safety. In the present study, the effects of the combination of OA and 5-fluorouracil (5-FU) on Panc-28 human pancreatic cells were studied. The results showed that combined use of OA and 5-FU synergistically potentiated cell death effects on Panc-28 cells, and the pro-apoptotic effects were also increased. Further study revealed that the combined treatment could enhance mitochondrial depolarization, lysosomal membrane permeabilization (LMP) and leakage of cathepin D, while the release of cytochrome C did not display significant changes. The expression of apoptosis related proteins was also affected in cells treated with the combination of OA and 5-FU, including activation of caspases-3 and the expression of Bcl-2/Bax, survivin and NF-κB. Our results provide evidence that combination of OA and 5-FU may serve as a novel strategy for the treatment of pancreatic cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics. CA Cancer J Clin. 60:277–300. 2010.

2 

Chua YJ and Zalcberg JR: Pancreatic cancer-is the wall crumbling? Ann Oncol. 119:1224–1230. 2008. View Article : Google Scholar

3 

Pierantoni C, Pagliacci A, Scartozzi M, Berardi R, Bianconi M and Cascinu S: Pancreatic cancer: progress in cancer therapy. Crit Rev Oncol Hematol. 67:27–38. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Hwang PM, Bunz F, Yu J, Rago C, et al: Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells. Nat Med. 7:1111–1117. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Malet-Martino M and Martino R: Clinical studies of three oral prodrugs of 5-fluorouracil (Capecitabine, UFT, S-1): a review. Oncologist. 7:288–323. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Li D, Xie K, Wolff R and Abbruzzese JL: Pancreatic cancer. Lancet. 363:1049–1057. 2004. View Article : Google Scholar

7 

Borja-Cacho D, Yokoyama Y, Chugh RK, et al: TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells. J Gastrointest Surg. 14:252–260. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Dizaji MZ, Malehmir M, Ghavamzadeh A, Alimoghaddam K and Ghaffari SH: Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line. Neurochem Res. 37:370–380. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Menéndez JA, Barbacid MM, Montero S, et al: Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur J Cancer. 37:402–413. 2001.PubMed/NCBI

10 

Nakagawa T, Shimizu M, Shirakami Y, et al: Synergistic effects of acyclic retinoid and gemcitabine on growth inhibition in pancreatic cancer cells. Cancer Lett. 273:250–256. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Yagi1 H, Yotsumoto F, Sonoda1 K, Kuroki M, Mekada E and Miyamoto S: Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer. Int J Cancer. 124:1429–1439. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Sei S, Mussio JK, Yang Q, et al: Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells. Mol Cancer. View Article : Google Scholar : 2009.PubMed/NCBI

13 

Liu J: Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol. 100:92–94. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Wang X, Ye X, Liu R, et al: Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases. Chem Biol Interact. 184:328–337. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Rubén M, Juliana CT, Marita, Mercedes A, Valentina RG and María LN: Beneficial actions of oleanolic acid in an experimental model of multiple sclerosis: a potential therapeutic role. Biochem Pharmacol. 79:198–208. 2010.PubMed/NCBI

16 

Teodoro T, Zhang L, Alexander T, Yue J, Vranic M and Volchuk A: Oleanolic acid enhances insulin secretion in pancreatic β-cells. FEBS Lett. 582:1375–1380. 2008.PubMed/NCBI

17 

Resende FA, Barcala CA, Faria MC, Kato FH, Cunha WR and Tavares DC: Antimutagenicity of ursolic acid and oleanolic acid against doxorubicin-induced clastogenesis in Balb/c mice. Life Sci. 79:1268–1273. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Liu J: Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol. 49:57–68. 1995. View Article : Google Scholar : PubMed/NCBI

19 

Wei J, Liu M, Liu H, et al: Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells. J Appl Toxicol. (In press).

20 

Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI

21 

Mai Z, Blackburn GL and Zhou J: Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice. Carcinogenesis. 28:1217–1223. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Mao CY, Hua HJ, Chen P, Yu DC, Cao J and Teng LS: Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFP expressing hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 8:282–287. 2009.PubMed/NCBI

23 

Chou TC and Talalay P: Analysis of combined drug effects: a new look at a very old problem. Trends Pharmacol Sci. 4:450–454. 1983. View Article : Google Scholar

24 

Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI

25 

Luo M, Liu X, Zua Y, Fu Y, Zhang S, Yao L and Efferth T: Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L. ) Millsp] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway. Chem Biol Interact. 188:151–160. 2010.PubMed/NCBI

26 

Ning X, Zhao J, Zhang Y, Cao S, Liu M, Ling P and Lin X: A novel anti-tumor protein extracted from Meretrix meretrix Linnaeus induces cell death by increasing cell permeability and inhibiting tubulin polymerization. Int J Oncol. 35:805–812. 2009.PubMed/NCBI

27 

Cao J, Liu Y, Jia L, et al: Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. Free Radic Biol Med. 43:968–975. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Averette KM, Pratt MR, Yang Y, et al: Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent. PLoS One. 4:e79132009. View Article : Google Scholar : PubMed/NCBI

29 

Zhang Y, Yang S, Liu M, et al: Interaction between thymidylate synthase and its cognate mRNA in zebrafish embryos. PLoS One. 5:e106182010. View Article : Google Scholar : PubMed/NCBI

30 

Tong D, Poot M, Hu D and Oda D: 5-fluorouracil-induced apoptosis in cultured oral cancer cells. Oral Oncol. 36:236–241. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Warr JR, Bamford A and Quinn DM: The preferential induction of apoptosis in multidrug-resistant KB cells by 5-fluorouracil. Cancer Lett. 175:39–44. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Sugamura K, Makino M, Shirai H, Kimura O, Maeta M, Itoh H and Kaibara N: Enhanced induction of apoptosis of human gastric carcinoma cells after preoperative treatment with 5-fluorouracil. Cancer. 79:12–17. 1997. View Article : Google Scholar : PubMed/NCBI

33 

Feng L, Au-Yeung W, Xu YH, Wang SS, Zhu Q and Xiang P: Oleanolic acid from Prunella Vulgaris L. induces SPC-A-1 cell line apoptosis via regulation of Bax, Bad and Bcl-2 expression. Asian Pac J Cancer Prev. 12:403–408. 2011.PubMed/NCBI

34 

Shyu MH, Kao TC and Yen GC: Oleanolic acid and ursolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP. J Agric Food Chem. 58:6110–6118. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Hishita T, Tada-Oikawa S, Tohyama K, et al: Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis in myelodysplastic syndrome-derived cell line P39. Cancer Res. 61:2878–2884. 2001.PubMed/NCBI

36 

Reiners JJ, Caruso JA, Mathieu P, Chelladurai B, Yin XM and Kessel D: Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage. Cell Death Differ. 9:934–944. 2002. View Article : Google Scholar : PubMed/NCBI

37 

Servais H, van Der Smissen P, Thirion G, van der Essen G, van Bambeke F, Tulkens PM and Mingeot-Leclercq MP: Gentamicin-induced apoptosis in LLC-PK1 cells: involvement of lysosomes and mitochondria. Toxicol Appl Pharm. 206:321–333. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Bian X, McAllister-Lucas LM, Shao F, et al: NF-kappa B activation mediates doxorubicin-induced cell death in N-type neuroblastoma cells. J Biol Chem. 276:48921–48929. 2001. View Article : Google Scholar : PubMed/NCBI

39 

Dutta J, Fan Y, Gupta N, Fan G and Gélinas C: Current insights into the regulation of programmed cell death by NF-κB. Oncogene. 25:6800–6816. 2006.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wei J, Liu H, Liu M, Wu N, Zhao J, Xiao L, Han L, Chu E and Lin X: Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells. Oncol Rep 28: 1339-1345, 2012.
APA
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L. ... Lin, X. (2012). Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells. Oncology Reports, 28, 1339-1345. https://doi.org/10.3892/or.2012.1921
MLA
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L., Han, L., Chu, E., Lin, X."Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells". Oncology Reports 28.4 (2012): 1339-1345.
Chicago
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L., Han, L., Chu, E., Lin, X."Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells". Oncology Reports 28, no. 4 (2012): 1339-1345. https://doi.org/10.3892/or.2012.1921
Copy and paste a formatted citation
x
Spandidos Publications style
Wei J, Liu H, Liu M, Wu N, Zhao J, Xiao L, Han L, Chu E and Lin X: Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells. Oncol Rep 28: 1339-1345, 2012.
APA
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L. ... Lin, X. (2012). Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells. Oncology Reports, 28, 1339-1345. https://doi.org/10.3892/or.2012.1921
MLA
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L., Han, L., Chu, E., Lin, X."Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells". Oncology Reports 28.4 (2012): 1339-1345.
Chicago
Wei, J., Liu, H., Liu, M., Wu, N., Zhao, J., Xiao, L., Han, L., Chu, E., Lin, X."Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells". Oncology Reports 28, no. 4 (2012): 1339-1345. https://doi.org/10.3892/or.2012.1921
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