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Apoptosis

, Volume 13, Issue 6, pp 782–789 | Cite as

The bisphosphonate zoledronic acid inhibits the growth of HCT-116 colon carcinoma cells and induces tumor cell apoptosis

  • Lilian Sewing
  • Florian SteinbergEmail author
  • Harald Schmidt
  • Rüdiger Göke
Original Paper

Abstract

Besides its preventive action on bone resorption the third generation bisphosphonate zoledronic acid (ZOL) has been shown to display potent inhibitory action on the formation of bone metastases of various human cancers. Recent research also indicates an antitumoral effect on primary tumors and visceral metastases. Here we investigate for the first time the effect of ZOL on the human colon carcinoma cell line HCT-116. ZOL strongly inhibited the proliferation and soft agar colony formation of HCT-116 cells and caused a G1 cell cycle arrest in a population of ZOL treated cells. This cell cycle arrest was accompanied by an induction of apoptosis via a caspase dependent mechanism. Activation of Caspases 3, 7, 8 and 9, cleavage of PARP as well as the release of cytochrome C into the cytosol were detected in HCT-116 cells treated with low micromolar concentrations of ZOL. The induction of the mitochondrial pathway of apoptosis was accompanied by a translocation of Bax into the mitochondria, Bid activation and a decrease of overall Bcl-2 expression. We also detected a cytosolic increase of apoptosis inducing factor (AIF), a trigger of caspase-independent apoptosis. Taken together, our data indicate a potent antitumoral and apoptosis inducing effect of ZOL on HCT-116 colon carcinoma cells.

Keywords

Zoledronic acid Apoptosis Colon carcinoma HCT-116 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Lilian Sewing
    • 1
  • Florian Steinberg
    • 2
    Email author
  • Harald Schmidt
    • 1
  • Rüdiger Göke
    • 1
  1. 1.Clinical Research Unit for Gastrointestinal EndocrinologyUniversity of MarburgMarburgGermany
  2. 2.DKF RheumatologyUniversity of BernBernSwitzerland

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