Cellular pharmacology, antineoplastic activity and low in vivo toxicity of a carboxylato-bridged platinum(II) complex bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate.
The dinuclear platinum complex bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate has been previously shown to exert profound cytotoxicity in diverse tumor cell lines, while being far less detrimental than the clinically applied platinum drugs against some susceptible to platinum toxicity non-malignant cellular populations. In the present study we report the investigation of the cellular accumulation kinetics and apoptosis induction of the dinuclear complex in K-562, its potent in vivo antineoplastic activity against L1210 leukemia and Lewis lung carcinoma tumor models and its lower nephrotoxicity, myelosuppressive potential and clastogenicity in vivo relative to cisplatin.
Momekov
Georgi
G
Lab. of Cellular and Molecular Pharmacology, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University-Sofia, Bulgaria. gmomekov@satline.net
Konstantinov
Spiro
S
Topashka-Ancheva
Margarita
M
Bakalova
Adriana
A
Arpadjan
Sonja
S
Karaivanova
Margarita
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D002869:Chromosome Aberrations / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D020014:K562 Cells; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000633:toxicity; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009153:Mutagens; D009944:Organoplatinum Compounds; C519466:bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate