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- Title
Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk.
- Authors
Qi, Lian-Wen; Zhang, Zhiyu; Zhang, Chun-Feng; Anderson, Samantha; Liu, Qun; Yuan, Chun-Su; Wang, Chong-Zhi
- Abstract
Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger ( Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21waf1/cip1 and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53-/- and p53+/+ HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.
- Subjects
ANIMAL experimentation; APOPTOSIS; BIOLOGICAL models; BIOPHYSICS; CELL cycle; CELL physiology; CHEMOPREVENTION; COLON tumors; GINGER; LUMINESCENCE spectroscopy; MASS spectrometry; RESEARCH methodology; MICE; MOLECULAR structure; POLYMERASE chain reaction; PROTEIN kinases; RESEARCH funding; T-test (Statistics); WESTERN immunoblotting; PLANT extracts; DATA analysis software; PROTEIN kinase inhibitors; DESCRIPTIVE statistics
- Publication
American Journal of Chinese Medicine, 2015, Vol 43, Issue 4, p743
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X15500469