Mechanism of action of tetra-mu-carboxylatodirhodium(II) in L1210 tumor suspension culture.
The effect of tetrakis-mu-methoxyacetato, tetra-mu-acetato, tetra-mu-propionato, and tetra-mu-butyratodirhodium(II) on the proliferation and macromolecular synthesis of leukemia L1210 cells in suspension culture was evaluated. The cytotoxicity of these dimeric rhodium(II) complexes to tumor cells in suspension culture follows the same trend as observed in vivo, i.e., butyrato greater than propionato greater than acetato greater than methoxyacetato. The cellular synthesis of DNA and protein was found to be strongly inhibited by tetra-mu-propionatodirhodium(II), whereas minimal inhibition of RNA synthesis was observed. Flow microfluorometric analysis of the drug-treated cells revealed an arrest of cellular development during the G2 phase of the cell cycle. The inhibition of DNA synthesis was attributed at least in part to the arrest in G2 which is consistent with the observed inhibition of protein synthesis.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D007399:Interphase; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009942:Organometallic Compounds / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012238:Rhodium / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009942:Organometallic Compounds; D012334:RNA, Neoplasm; D012238:Rhodium