title: Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma Cells.
abstract: Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, β-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of α-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death.
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences,  Karl-Franzens University , Graz 8010, Austria.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kretschmer
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Deutsch
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.forename: Heike
authors.initials: H
authors.lastname: Knausz
authors.forename: Olaf
authors.initials: O
authors.lastname: Kunert
authors.forename: Martina
authors.initials: M
authors.lastname: Blunder
authors.forename: Herbert
authors.initials: H
authors.lastname: Boechzelt
authors.forename: Helmut
authors.initials: H
authors.lastname: Schaider
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D028082:Boraginaceae / Q000737:chemistry*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D053148:Caspase 3; D053179:Caspase 7