title: Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk.
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 p21(waf1/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.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing JS 210009, China.|Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago IL 60637, USA.
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Qi
authors.affiliation: Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago IL 60637, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing JS 210009, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago IL 60637, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Anderson
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing JS 210009, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago IL 60637, USA.|Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago IL 60637, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.affiliation: Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Chicago IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D008517:Phytotherapy; D020239:Receptor Cross-Talk; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002396:Catechols; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C040115:shogaol; D016203:CDC2 Protein Kinase; C517005:Cdc25a protein, mouse; D020687:cdc25 Phosphatases
keywords: 6-Shogaol; Apoptosis; Cell Cycle Arrest; Colorectal Cancer; Xenograft Tumor Model; Zingiber officinale; cdc2/cdc25A; p53/p21