Selective Cytotoxicity of the New Platnum ( 2 ) Complexes on Human Gastric Cancer Cell - lines and Normal Kidney Cells.
- Author:
Jee Chang JUNG
;
Sung Goo CHANG
;
Young Soo RHO
- Publication Type:In Vitro ; Original Article
- Keywords:
Selective cytotoxicity;
Platinum (II) complex;
Nephrotoxicity
- MeSH:
Adenocarcinoma;
Cell Survival;
Cisplatin;
Drug Discovery;
Glucose;
Humans*;
Kidney*;
Platinum;
Stomach Neoplasms*;
Thymidine
- From:Journal of the Korean Cancer Association
1999;31(5):1035-1043
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Platinum coordination complex (cisplatin) has been currently used as one of the most effective compound in the treatment of various solid tumors. However, its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and selective cytotoxicity. MATERIALS AND METHODS: A new series of highly water soluble platinum (II) complexes Pt (II) [1,3-Bis (phenylthio) propane) (trans-l-1,2-diaminocyclohexane) (PC-1) and Pt (II) [1,3-Bis-(phenylthio) (propane)]-1,2-diaminocyclohexane (PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (.IR), ""C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity and nephrotoxi -cities of new Pt (II) complexes were tested against MKN-45 human gastric cancer cell- lines and normal kidney cells using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl tetrazolium bromide] assay for cell survival and proliferation. RESULTS: PC-1 showed activity against MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cells, and the antitumor activity of this compound was comparable or superior to that of PC-2 and cisplatin. The nephrotoxicity of PC-1 and PC-2 were found quite less than that of cisplatin using MTT, [H] thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. CONCLUSION: Based on these results, this novel platinum (II) complex compound (PC-1) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.
