Melleolides induce rapid cell death in human primary monocytes and cancer cells
| Autor: | Oliver Werz, Olga Scherer, Markus Bohnert, Dirk Hoffmeister, Hans-Martin Dahse, Stefanie König, Katja Wiechmann |
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| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
Cell Survival Clinical Biochemistry Pharmaceutical Science Apoptosis Biochemistry Monocytes Structure-Activity Relationship Drug Discovery medicine Cytotoxic T cell Staurosporine Humans Cytotoxicity Molecular Biology Cells Cultured Microscopy biology Chemistry Organic Chemistry Armillaria mellea biology.organism_classification Cell biology Cell culture Cancer cell Cancer research Molecular Medicine K562 Cells Oligopeptides medicine.drug HeLa Cells |
| Zdroj: | Bioorganicmedicinal chemistry. 22(15) |
| ISSN: | 1464-3391 |
| Popis: | 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 (within1 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. |
| Databáze: | OpenAIRE |
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