Investigations on the effects of cobalt-alkyne complexes on leukemia and lymphoma cells: cytotoxicity and cellular uptake.
Cobalt-alkyne complexes represent a new class of antiproliferative drugs with high activity on cell lines derived from human solid tumors. These promising results encouraged us to evaluate also their effects against leukemia and lymphoma cells. For this purpose, we selected three cobalt complexes with (2-propyn-1-yl)acetylsalicylate (Co-ASS), 2-propyn-1-ol (Co-Prop) and diphenylacetylene (Co-Diph) ligands and investigated their growth inhibiting properties on the LAMA-84, K-562, SD-1 leukemia and U-937 lymphoma cell lines. The cobalt complexes showed high effects on LAMA-84 cells (IC(50)=7.7-16.8 microM) after 48 and 72 h of incubation, but were inactive (K-562, U-937) or low active (SD-1) on the other cell lines. The proliferation of SD-1 cells was reduced by Co-Prop (IC(50)=18.6 microM) and Co-Diph (IC(50)=7.5 microM) only after a 72 h exposure. The antiproliferative effects did not correlate with the accumulation of the drugs into the tumor cells. The time dependent uptake during 24 h determined by atomic absorption spectroscopy was comparably the same in sensitive LAMA-84 and insensitive K-562 cells.
Ott
Ingo
I
Institute of Pharmacy, Free University of Berlin, Germany.
Kircher
Brigitte
B
Gust
Ronald
R
D000480:Alkynes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic; D020298:U937 Cells
D000480:Alkynes; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D003035:Cobalt