title: Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells.
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.
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors: Xiang
authors: X
authors: Gao
authors: Bo
authors: B
authors: Jiang
authors: Shitao
authors: S
authors: Zou
authors: Ting
authors: T
authors: Zhang
authors: Xiaowei
authors: X
authors: Qi
authors: Linfang
authors: L
authors: Jin
authors: Xiaosong
authors: X
authors: Ge
authors: Shou-Ching
authors: SC
authors: Tang
authors: Dong
authors: D
authors: Hua
authors: Weichang
authors: W
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage*; D045325:HCT116 Cells; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid