Chemotherapeutic Drugs Inhibit Ribosome Biogenesis at Various Levels
作者： Kaspar Burger , Bastian Mühl , Thomas Harasim , Michaela Rohrmoser , Anastassia Malamoussi
关键词: RRNA processing 、 Ribosomal RNA 、 RRNA transcription 、 Homoharringtonine 、 Ribosome 、 Biology 、 Ribosome biogenesis 、 Pharmacology 、 Molecular biology 、 RNA 、 Nucleolus
摘要: Drugs for cancer therapy belong to different categories of chemical substances. The cellular targets the therapeutic efficacy are often not unambiguously identified. Here, we describe process ribosome biogenesis as a target large variety chemotherapeutic drugs. We determined inhibitory concentration 36 drugs transcription and processing ribosomal RNA by in vivo labeling experiments. Inhibitory drug concentrations were correlated loss nucleolar integrity. synergism inhibiting synthesis at levels was studied. inhibited either level (i) rRNA (e.g. oxaliplatin, doxorubicin, mitoxantrone, methotrexate), (ii) early camptothecin, flavopiridol, roscovitine), or (iii) late 5-fluorouracil, MG-132, homoharringtonine). Blockage steps caused disintegration, whereas blockage left nucleolus intact. Flavopiridol 5-fluorouracil showed strong inhibition processing. conclude that potentially may contribute regimens.
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