In vitro cytotoxicity of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol in rat hepatoma AH-109A cells and human tumor cell lines.
SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N ')bis(myristato)] platinum(II), is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was shown to have antitumor activity against hepatic tumors after intra-hepatic arterial administration in animal models. In this study, the in vitro growth inhibitory activities of SM-11355 and cisplatin (CDDP) following 7-d drug exposure were examined using rat ascite hepatoma AH-109A cells and various human tumor cell lines. In monolayer or suspension cell cultures, SM-11355 did not inhibit the cell growth, whereas SM-11355/Lipiodol had dose-dependent growth inhibitory activities, as did CDDP suspended in Lipiodol (CDDP/Lipiodol). This was also the case in the colony formation assay in agarose gel. CDDP/Lipiodol released platinum compound into the culture medium rapidly, whereas SM-11355/Lipiodol released it slowly but constantly for 7 d. Furthermore, a significant amount of platinum was detected in the cells treated with CDDP/Lipiodol and SM-11355/Lipiodol. These results suggest that Lipiodol plays an important role in the in vitro cytotoxicity of SM-11355, and certain platinum compounds released from SM-11355/Lipiodol have growth inhibitory effects on these cells.
Kishimoto
S
S
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Noguchi
T
T
Yamaoka
T
T
Fukushima
S
S
Takeuchi
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003470:Culture Media; D004337:Drug Carriers; D006801:Humans; D007459:Iodized Oil; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003470:Culture Media; D004337:Drug Carriers; D009944:Organoplatinum Compounds; C406530:miriplatin; D007459:Iodized Oil