title: Induction of apoptosis in HL-60 cells through the ROS-mediated mitochondrial pathway by ramentaceone from Drosera aliciae.
abstract: Ramentaceone (1) is a naphthoquinone constituent of Drosera aliciae that exhibits potent cytotoxic activity against various tumor cell lines. However, its molecular mechanism of cell death induction has still not been determined. The present study demonstrates that 1 induces apoptosis in human leukemia HL-60 cells. Typical morphological and biochemical features of apoptosis were observed in 1-treated cells. Compound 1 induced a concentration-dependent increase in the sub-G1 fraction of the cell cycle. A decrease in the mitochondrial transmembrane potential (ΔΨm) was also observed. Furthermore, 1 reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and Bak, induced cytochrome c release, and increased the activity of caspase 3. The generation of reactive oxygen species (ROS) was detected in 1-treated HL-60 cells, which was attenuated by the pretreatment of cells with a free radical scavenger, N-acetylcysteine (NAC). NAC also prevented the increase of the sub-G1 fraction induced by 1. These results indicate that ramentaceone induces cell death through the ROS-mediated mitochondrial pathway.
authors.affiliation: Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland. kawiak@biotech.ug.gda.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kawiak
authors.forename: Joanna
authors.initials: J
authors.lastname: Zawacka-Pankau
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wasilewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Stasilojc
authors.forename: Jacek
authors.initials: J
authors.lastname: Bigda
authors.forename: Ewa
authors.initials: E
authors.lastname: Lojkowska
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D029787:Drosera / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C517013:7-methyljuglone; D000972:Antineoplastic Agents, Phytogenic; D016166:Free Radical Scavengers; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000111:Acetylcysteine