Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells

Xiang Gao, Bo Jiang, Shitao Zou, Ting Zhang, Xiaowei Qi, Linfang Jin, Xiaosong Ge, Shou Ching Tang, Dong Hua, Weichang Chen

Research output: Contribution to journalArticle

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Abstract

Zoledronate (ZOL) is a third-generation bisphosphonate (BP), clinically used to treat lytic bone lesions caused by malignancies or bone resorption disorders. Mechanistically, ZOL was recently shown to have direct pro-apoptotic effects on tumor cells and to inhibit cancer cell invasion, adhesion, proliferation, and angiogenesis. The molecular mechanism of ZOL-induced apoptosis remains unknown. In this study, we observed that ZOL induced apoptosis in colorectal cancer cells HCT116 and Caco-2. After HCT116 and Caco-2 cells were treated with ZOL, decreased fluorescence of JC-1 aggregates (590 nm) was seen in mitochondria. Western blotting analysis showed that cytochrome c was decreased in the mitochondria and increased in the cytosol, respectively. The effects were dependent on the concentration and treatment time by ZOL. In vivo experiments showed that ZOL inhibited the growth of xenograft tumor in mice. Hematoxylin and eosin (H&E) staining of tissue samples showed a significantly increased apoptosis body in the ZOL-treated xenografts compared to control. Taken together, our data demonstrated that ZOL inhibits growth of HCT116 cells both in vitro and in vivo and induce apoptosis through the mitochondria pathway.

Original languageEnglish (US)
Pages (from-to)5315-5322
Number of pages8
JournalTumor Biology
Volume36
Issue number7
DOIs
StatePublished - Jul 29 2015

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zoledronic acid
Colorectal Neoplasms
Apoptosis
Mitochondria
Caco-2 Cells
Heterografts
Neoplasms
HCT116 Cells
Diphosphonates

Keywords

  • Colorectal cancer
  • Mitochondria apoptosis pathway
  • Zoledronate

ASJC Scopus subject areas

  • Cancer Research

Cite this

Gao, X., Jiang, B., Zou, S., Zhang, T., Qi, X., Jin, L., ... Chen, W. (2015). Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells. Tumor Biology, 36(7), 5315-5322. https://doi.org/10.1007/s13277-015-3192-x

Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells. / Gao, Xiang; Jiang, Bo; Zou, Shitao; Zhang, Ting; Qi, Xiaowei; Jin, Linfang; Ge, Xiaosong; Tang, Shou Ching; Hua, Dong; Chen, Weichang.

In: Tumor Biology, Vol. 36, No. 7, 29.07.2015, p. 5315-5322.

Research output: Contribution to journalArticle

Gao, X, Jiang, B, Zou, S, Zhang, T, Qi, X, Jin, L, Ge, X, Tang, SC, Hua, D & Chen, W 2015, 'Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells', Tumor Biology, vol. 36, no. 7, pp. 5315-5322. https://doi.org/10.1007/s13277-015-3192-x
Gao, Xiang ; Jiang, Bo ; Zou, Shitao ; Zhang, Ting ; Qi, Xiaowei ; Jin, Linfang ; Ge, Xiaosong ; Tang, Shou Ching ; Hua, Dong ; Chen, Weichang. / Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells. In: Tumor Biology. 2015 ; Vol. 36, No. 7. pp. 5315-5322.
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