Relation between intracellular accumulation and cytotoxic activity of cis-[((1R, 2R)-1, 2-cyclohexanediamine-N, N')bis(myristato)]platinum(II) suspended in Lipiodol.
SM-11355, cis-[((1R, 2R)-1, 2-cyclohexanediamine-N, N')bis(myristato)]platinum(II), suspended in Lipiodol (SM-11355/Lipiodol) showed cytotoxic activity in hepatic tumor models in vivo and tumor cell lines in vitro. SM-11355/Lipiodol demonstrated selective retention in tumor tissue in vivo and high accumulation in tumor cells in vitro. This study was aimed to clarify the relation between the cytotoxicity of SM-11355/Lipiodol and intracellular platinum content. The cytotoxic activities were estimated by using WST-1 reagent. Intracellular platinum content and platinum-DNA adduct were estimated following exposure with SM-11355/Lipiodol when methionine was added. Methionine clearly inhibited the cytotoxic activities of SM-11355/Lipiodol. Moreover, intracellular platinum content and platinum-DNA adduct following exposure of SM-11355/Lipiodol decreased with increases in methionine concentration. The characteristic release of SM-11355/Lipiodol was not affected by addition of methionine. The present results suggested that one of platinum compounds exposed to cells following SM-11355/Lipiodol treatment is very similar in cytotoxic mechanism to cisplatin.
Kishimoto
Shuichi
S
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Arise Ikawadani-cho, Nishi-ku, Japan. skisimot@pharm.kobegakuin.ac.jp
Ohtani
Aya
A
Fukuda
Hisayuki
H
Fukushima
Shoji
S
Takeuchi
Yoshikazu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D004347:Drug Interactions; D007459:Iodized Oil; D008715:Methionine / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004337:Drug Carriers; D009944:Organoplatinum Compounds; C406530:miriplatin; D007459:Iodized Oil; D008715:Methionine