title: Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic MOLT-4 cell line by terpinen-4-ol.
abstract: Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Patompong
authors.initials: P
authors.lastname: Khaw-on
authors.forename: Ratana
authors.initials: R
authors.lastname: Banjerdpongchai
mesh_terms: D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011419:Propidium / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013729:Terpenes; D011419:Propidium; C034019:terpinenol-4; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8