title: Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC.
abstract: The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shen-Jeu
authors.initials: SJ
authors.lastname: Won
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Cheng-Hsin
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Jiang-Shieh
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Lin
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Jyun-Ti
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chun-Li
authors.identifier: http://orcid.org/0000-0001-7617-2077
authors.initials: CL
authors.lastname: Su
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000071192:Autophagy-Related Protein 12 / Q000235:genetics / Q000378:metabolism; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; D000972:Antineoplastic Agents, Phytogenic; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; D012333:RNA, Messenger; D014315:Triterpenes; C573355:garcinielliptone FC; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: apoptosis; autophagy; garcinielliptone FC; human colorectal cancer