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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
November-2019 Volume 18 Issue 5

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
November-2019 Volume 18 Issue 5

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

Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate

  • Authors:
    • Benjaporn Buranrat
    • Auemduan Prawan
    • Laddawan Senggunprai
    • Veerapol Kukongviriyapan
  • View Affiliations / Copyright

    Affiliations: Faculty of Medicine, Mahasarakham University, Muang, MahaSarakham 44000, Thailand, Department of Pharmacology, Faculty of Medicine, KhonKaen University, KhonKaen 40002, Thailand
    Copyright: © Buranrat et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3977-3983
    |
    Published online on: September 23, 2019
       https://doi.org/10.3892/etm.2019.8041
  • 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

Pamidronate has been hypothesized to effectively inhibit cancer cell growth and metastasis in bone tissue. Furthermore, pamidronate (Pami) exerts various direct effects against several cancer cell types, including growth and migration. The present study aimed to determine the underlying mechanism of Pami's effect on the proliferation and migration of cholangiocarcinoma (CCA) cells. KKU‑100 cells were used to determine the effects of Pami on cell death and migration. The following were assessed: Sulforhodamine B, colony formation, apoptosis via flow cytometry, reactive oxygen species (ROS) production and caspase‑3 activity. In addition, the effects of the test compound on the mevalonate (MVA) signaling pathway were determined via western blotting and reverse transcription‑quantitative PCR. Cell migration was observed via wound healing, Matrigel and gelatin zymography. The results indicated that Pami induced CCA cell death and inhibited colony formation in a dose‑dependent manner, with IC50 values of 444.67±44.05 µM at 24 h and 147.33±17.01 µM at 48 h. Furthermore, Pami treatment suppressed colony formation at a lower concentration than growth inhibition with IC50 values of 5.36±0.31 µM. The mechanism of growth inhibition was determined to potentially be associated with increased ROS generation and stimulated caspase‑3 enzyme activity, leading to the induction of apoptosis. Furthermore, Pami treatment interfered with the MVA signaling pathway by reducing Rac1 protein levels and modulating the gene and protein expression of RhoA. Furthermore, Pami suppressed CCA cell migration by decreasing matrix metalloproteinase (MMP)2 and MMP9 levels. Additionally, Pami treatment activated CCA cell death and inhibited CCA migration at low concentrations. Pami significantly decreased the protein expression levels of Rac1 in the MVA signaling pathway and may therefore be beneficial for developing a novel chemotherapeutic method for CCA.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Fleisch H: Development of bisphosphonates. Breast Cancer Res. 4:30–34. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Iguchi K, Tatsuda Y, Usui S and Hirano K: Pamidronate inhibits antiapoptotic bcl-2 expression through inhibition of the mevalonate pathway in prostate cancer PC-3 cells. Eur J Pharmacol. 641:35–40. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Iguchi T, Miyakawa Y, Saito K, Nakabayashi C, Nakanishi M, Saya H, Ikeda Y and Kizaki M: Zoledronate-induced S phase arrest and apoptosis accompanied by DNA damage and activation of the ATM/Chk1/cdc25 pathway in human osteosarcoma cells. Int J Oncol. 31:285–291. 2007.PubMed/NCBI

4 

Molinuevo MS, Bruzzone L and Cortizo AM: Alendronate induces anti-migratory effects and inhibition of neutral phosphatases in UMR106 osteosarcoma cells. Eur J Pharmacol. 562:28–33. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjällman AH, Ballmer-Hofer K and Schwendener RA: Clodronate-liposome-mediated depletion of tumour-associated macrophages: A new and highly effective antiangiogenic therapy approach. Br J Cancer. 95:272–281. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, et al: Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 360:679–691. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Asahi H, Mizokami A, Maeda Y, Komatsu K, Koshida K and Namiki M: Bisphosphonate therapy for hormone refractory prostate cancer with bone metastasis. J Urol. 169:281–282. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW and Finkelstein JS: Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med. 345:948–955. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Boissier S, Ferreras M, Peyruchaud O, Magnetto S, Ebetino FH, Colombel M, Delmas P, Delaissé JM and Clézardin P: Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res. 60:2949–2954. 2000.PubMed/NCBI

10 

Iguchi K, Matsunaga S, Nakano T, Usui S and Hirano K: Inhibition of caveolin-1 expression by incadronate in PC-3 prostate cells. Anticancer Res. 26:2977–2981. 2006.PubMed/NCBI

11 

Nishida S, Fujii Y, Yoshioka S, Kikuichi S, Tsubaki M and Irimajiri K: A new bisphosphonate, YM529 induces apoptosis in HL60 cells by decreasing phosphorylation of single survival signal ERK. Life Sci. 73:2655–2664. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Asahi H, Mizokami A, Miwa S, Keller ET, Koshida K and Namiki M: Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells. Int J Urol. 13:593–600. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Valenti MT, Bertoldo F, Dalle Carbonare L, Azzarello G, Zenari S, Zanatta M, Balducci E, Vinante O and Lo Cascio V: The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene? BMC Cancer. 6:492006. View Article : Google Scholar : PubMed/NCBI

14 

Oades GM, Senaratne SG, Clarke IA, Kirby RS and Colston KW: Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate pathway, impairing Ras membrane localization in prostate cancer cells. J Urol. 170:246–252. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Virtanen SS, Väänänen HK, Härkönen PL and Lakkakorpi PT: Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Cancer Res. 62:2708–2714. 2002.PubMed/NCBI

16 

Walker K and Olson MF: Targeting Ras and Rho GTPases as opportunities for cancer therapeutics. Curr Opin Genet Dev. 15:62–68. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Zhang PL, Lun M, Siegelmann-Danieli N, Blasick TM and Brown RE: Pamidronate resistance and associated low ras levels in breast cancer cells: A role for combinatorial therapy. Ann Clin Lab Sci. 34:263–270. 2004.PubMed/NCBI

18 

Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, Bethony JM and Loukas A: The tumorigenic liver fluke Opisthorchis viverrini-multiple pathways to cancer. Trends Parasitol. 28:395–407. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Sookprasert A, Chindaprasert J and Wirasorn K: Systemic therapy for locally advanced and metastatic cholangiocarcinoma. Asian Pac J Cancer Prev. (Suppl 13):3–6. 2012.PubMed/NCBI

20 

Buranrat B, Mairuae N and Kanchanarach W: Cytotoxic and antimigratory effects of Cratoxy formosum extract against HepG2 liver cancer cells. Biomed Rep. 6:441–448. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Klungsaeng S, Kukongviriyapan V, Prawan A, Kongpetch S and Senggunprai L: Cucurbitacin B induces mitochondrial-mediated apoptosis pathway in cholangiocarcinoma cells via suppressing focal adhesion kinase signaling. Naunyn Schmiedebergs Arch Pharmacol. 392:271–278. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Chen H, Wang C, Qi M, Ge L, Tian Z, Li J, Zhang M, Wang M, Huang L and Tang X: Anti-tumor effect of Rhaponticum uniflorum ethyl acetate extract by regulation of peroxiredoxin1 and epithelial-to-mesenchymal transition in oral cancer. Front Pharmacol. 8:8702017. View Article : Google Scholar : PubMed/NCBI

23 

Buranrat B, Mairuae N and Konsue A: Cratoxy formosum leaf extract inhibits proliferation and migration of human breast cancer MCF-7 cells. Biomed Pharmacother. 90:77–84. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Bosco EE, Mulloy JC and Zheng Y: Rac1 GTPase: A ‘Rac’ of all trades. Cell Mol Life Sci. 66:370–374. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Yoshida T, Zhang Y, Rivera Rosado LA, Chen J, Khan T, Moon SY and Zhang B: Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol Cancer Ther. 9:1657–1668. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Miller T, Yang F, Wise CE, Meng F, Priester S, Munshi MK, Guerrier M, Dostal DE and Glaser SS: Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity. Dig Liver Dis. 43:395–403. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Kamigaki M, Sasaki T, Serikawa M, Inoue M, Kobayashi K, Itsuki H, Minami T, Yukutake M, Okazaki A, Ishigaki T, et al: Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells. Int J Oncol. 39:561–568. 2011.PubMed/NCBI

29 

Riebeling C, Forsea AM, Raisova M, Orfanos CE and Geilen CC: The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Br J Cancer. 87:366–371. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Wada A, Fukui K, Sawai Y, Imanaka K, Kiso S, Tamura S, Shimomura I and Hayashi N: Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 44:142–150. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Lai TJ, Hsu SF, Li TM, Hsu HC, Lin JG, Hsu CJ, Chou MC, Lee MC, Yang SF and Fong YC: Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line. Acta Pharmacol Sin. 28:1231–1235. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Heikkilä P, Teronen O, Moilanen M, Konttinen YT, Hanemaaijer R, Laitinen M, Maisi P, van der Pluijm G, Bartlett JD, Salo T and Sorsa T: Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Anticancer Drugs. 13:245–254. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Ponce-Cusi R and Calaf GM: Antitumor activity of pamidronate in breast cancer cells transformed by low doses of α-particles and estrogen in vitro. Int J Oncol. 46:2663–2669. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Issat T, Nowis D, Legat M, Makowski M, Klejman MP, Urbanski J, Skierski J, Koronkiewicz M, Stoklosa T, Brzezinska A, et al: Potentiated antitumor effects of the combination treatment with statins and pamidronate in vitro and in vivo. Int J Oncol. 30:1413–1425. 2007.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Buranrat B, Prawan A, Senggunprai L and Kukongviriyapan V: Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate. Exp Ther Med 18: 3977-3983, 2019.
APA
Buranrat, B., Prawan, A., Senggunprai, L., & Kukongviriyapan, V. (2019). Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate. Experimental and Therapeutic Medicine, 18, 3977-3983. https://doi.org/10.3892/etm.2019.8041
MLA
Buranrat, B., Prawan, A., Senggunprai, L., Kukongviriyapan, V."Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate". Experimental and Therapeutic Medicine 18.5 (2019): 3977-3983.
Chicago
Buranrat, B., Prawan, A., Senggunprai, L., Kukongviriyapan, V."Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate". Experimental and Therapeutic Medicine 18, no. 5 (2019): 3977-3983. https://doi.org/10.3892/etm.2019.8041
Copy and paste a formatted citation
x
Spandidos Publications style
Buranrat B, Prawan A, Senggunprai L and Kukongviriyapan V: Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate. Exp Ther Med 18: 3977-3983, 2019.
APA
Buranrat, B., Prawan, A., Senggunprai, L., & Kukongviriyapan, V. (2019). Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate. Experimental and Therapeutic Medicine, 18, 3977-3983. https://doi.org/10.3892/etm.2019.8041
MLA
Buranrat, B., Prawan, A., Senggunprai, L., Kukongviriyapan, V."Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate". Experimental and Therapeutic Medicine 18.5 (2019): 3977-3983.
Chicago
Buranrat, B., Prawan, A., Senggunprai, L., Kukongviriyapan, V."Inhibition of growth and migration of cholangiocarcinoma cells by pamidronate". Experimental and Therapeutic Medicine 18, no. 5 (2019): 3977-3983. https://doi.org/10.3892/etm.2019.8041
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