title: Koelreuteria Formosana Extract Induces Growth Inhibition and Cell Death in Human Colon Carcinoma Cells via G2/M Arrest and LC3-II Activation-Dependent Autophagy.
abstract: Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death. Exposed KFEE cells showed increased levels of acridine orange, autophagic vacuoles, and LC3-II proteins, which are specific autophagic markers. Bcl-2, p-Akt, and p-mTOR levels, which have been implicated in autophagic downregulation, were decreased after KFEE treatment. Autophagy inhibitor 3-methyladenosine and bafilomycin-A1 and genetic silencing of LC3 attenuated KFEE-induced growth inhibition. These findings suggested that KFEE causes cytostatic effect through autophagy. In xenograft studies, oral administration of KFEE had significantly inhibited the tumor growth in nude mice that had received subcutaneous injection of DLD-1 cells. KFEE is a promising candidate in phytochemical-based, mechanistic, and pathway-targeted cancer prevention strategies.
authors.affiliation: a Medical Education Center , Kaohsiung Armed Forces General Hospital , Kaohsiung , Taiwan.|b Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University , Taichung , Taiwan.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Horng
authors.affiliation: c Department of Colorectal surgery , Kaohsiung Armed Forces General Hospital , Kaohsiung , Taiwan.
authors.forename: Yueh-Jung
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: b Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University , Taichung , Taiwan.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.affiliation: d Institute and Department of Food Science, Central Taiwan University of Science and Technology , Taichung , Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.affiliation: b Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University , Taichung , Taiwan.
authors.forename: Chun-Miao
authors.initials: CM
authors.lastname: Tsai
authors.affiliation: b Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University , Taichung , Taiwan.|e Clinical Laboratory , Chung Shan Medical University Hospital , Taichung , Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D029631:Sapindaceae / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts