title: Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway.
abstract: Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated from Annonaceae plants. In this study, we purified annonacin, a cytotoxic mono-tetrahydrofuran acetogenin, from the seeds of Annona reticulata and analyzed its biological effects. Herein, we have shown that annonacin caused significant cell death in various cancer cell lines. T24 bladder cancer cells at the S phase were more vulnerable to the cytotoxicity of annonacin. Furthermore, annonacin activated p21 in a p53-independent manner and arrested T24 cells at the G1 phase. It also induced Bax expression, enhanced caspase-3 activity, and caused apoptotic cell death in T24 cells. In summary, these results suggest that annonacin is potentially a promising anti-cancer compound.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Medical University, Kaohsiung, Taiwan 807, ROC. yuanssf@ms33.hinet.net
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Chang
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Kuei-Hsiang
authors.initials: KH
authors.lastname: Lin
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Jinu-Huang
authors.initials: JH
authors.lastname: Su
mesh_terms: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005663:Furans / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051028:bcl-2-Associated X Protein
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D061945:Caspase Inhibitors; D005663:Furans; D007783:Lactones; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C053442:annonacin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine