[Pt(HPxSC)Cl(3)], a novel platinum(IV) compound with anticancer properties.
There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl(3)] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl(3)] markedly reduced the number of cultured astrocytoma cells (IC(50), 80 microM), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl(3)]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl(3)] at 200 microM did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC(50), 15 microM) and primary astrocytes (IC(50), 20 microM). Moreover, [Pt(HPxSC)Cl(3)] at 100 microM did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-alpha. Finally, we assessed the ability of [Pt(HPxSC)Cl(3)] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity.
Marković
Milos
M
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia and Montenegro.
Knezević
Nikola
N
Momcilović
Miljana
M
Grgurić-Sipka
Sanja
S
Harhaji
Ljubica
L
Trajković
Vladimir
V
Mostarica Stojković
Marija
M
Sabo
Tibor
T
Miljković
Djordje
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004273:DNA, Neoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D017671:Platinum Compounds / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma