title: Melleolides induce rapid cell death in human primary monocytes and cancer cells.
abstract: The melleolides are structurally unique and bioactive natural products of the basidiomycete genus Armillaria. Here, we report on cytotoxic effects of melleolides from Armillaria mellea towards non-transformed human primary monocytes and human cancer cell lines, respectively. In contrast to staurosporine or pretubulysin that are less cytotoxic for monocytes, the cytotoxic potency of the active melleolides in primary monocytes is comparable to that in cancer cells. The onset of the cytotoxic effects of melleolides was rapid (within <1 h), as compared to the apoptosis inducer staurosporine, the protein biosynthesis inhibitor cycloheximide, and the DNA transcription inhibitor actinomycin D (>5 h, each). Side-by-side comparison with the detergent triton X-100 and staurosporine in microscopic and flow cytometric analysis studies as well as analysis of the viability of mitochondria exclude cell lysis and apoptosis as relevant or primary mechanisms. Our results rather point to necrotic features of cell death mediated by an as yet elusive but rapid mechanism.
authors.affiliation: Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität Jena, Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bohnert
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Scherer
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Wiechmann
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: König
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.affiliation: Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität Jena, Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hoffmeister
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany. Electronic address: oliver.werz@uni-jena.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008853:Microscopy; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D019311:Staurosporine / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D019311:Staurosporine; C575012:pretubulysin
keywords: Cell death; Cytotoxicity; Monocytes; Natural products; Structure activity relationship