Calebin-A induces human colon cancer cell cycle arrest and inhibits tumor cell growth in vitro and in vivo
Date Issued
2015
Date
2015
Author(s)
Lin, Chen
Abstract
Calebin-A is a curcuminoids compound isolated from turmeric. Previous studies indicated that calebin-A inhibits cell growth and induces apoptosis in drug-resistant human gastric cancer cells and also restrain the proliferation of human hepatoma cell line HepG2 cells; however, the molecular mechanism of anti-cancer activity in colon cancer remains unclear. Therefore, the objectives of research are to study the anti-cancer efficacy of calebin-A and its underlying molecular mechanism. Furthermore, we use xenograft animal model to further investigate the anti-tumor effect of calebin-A. The results showed calebin-A was able to inhibit colon cancer cells growth and induced cell cycle to arrest in S and G2/M phase. At the molecular levels, calebin-A exhibited the anti-cancer ability by increasing reactive oxygen species (ROS) level and triggering DNA damage response as evidenced by flow cytometry and comet assay. Western blot analysis showed calebin-A up-regulation of phosphorylation of H2AX, chk1, chk2, p53 and p53, p21 protein levels, decreased cdc25A, cyclinB, cyclinA and cdc2 protein levels. Moreover, pretreatment of N-acetyl-L-cysteine (NAC) reversed the cell cycle population, indicated ROS might involve in the cell cycle arrest signaling pathway caused by the toxic of calebin-A. In the xenograft model, we evaluated the anti-tumor ability of calebin-A on HCT116 tumor xenografts in vivo. Intraperitoneal injection of calebin-A (25 mg/kg) to nude mice significantly decreased tumor volume as well as reduced tumor size and proliferating cell nuclear antigen (PCNA) protein by Hematoxylin & Eosin (HE) and immunohistochemistry (IHC) stain, respectively. These results suggested calebin-A with potent anti-cancer effect in vitro and in vivo, could provided a molecular basis for the development of colon cancer chemopreventive agent.
Subjects
cell cycle
colon cancer
curcuminoids
xenograft
SDGs
Type
thesis
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