Young-Ee Kwon1, Jung-Youl Park, Won-Kyu Kim. 1. College of Pharmacy, Woosuk University, Wanju-gun, Jeonbuk 565-701, Republic of Korea. yekwon@woosuk.ac.kr
Abstract
BACKGROUND: The newly synthesized octahedral Pt(IV) complex series showed potent antitumor activities, both in vitro and in vivo. Carboplatin, possessing a soluble leaving ligand, is known to be less toxic than cisplatin. The synthesized K104 is a Pt(IV) complex with a malonato leaving group and seven-membered ring structure between the central platinum and amine carrier ligands. In this study, the histoculture drug response assay (HDRA) of K104 on human cancer tissues was investigated in vitro and nephrotoxicity was examined in vivo. MATERIALS AND METHODS: Cytotoxicity was tested in various cancer cell lines, and the HDRA of K104 was evaluated by MTT assay in vitro using colorectal and breast cancer tissues from patients. In order to compare the nephrotoxicity of K104 with cisplatin and carboplatin, blood serum levels of BUN, creatinine and uric acid in ICR mice were measured. RESULTS: K104 showed more effective anticancer activities than carboplatin in most cancer cell lines. In HDRA, K104 showed a 50.0-66.7% efficacy rate compared with 33.3% of cisplatin and 58.3% of carboplatin against colorectal cancer patient tissues. In breast cancer tissues, K104 only showed an efficacy rate above 50%. The serum levels of BUN, creatinine and uric acid did not change after a single intraperitoneal administration of K104 (90 mg/kg) in ICR mice. CONCLUSION: K104 showed more effective anticancer activities than carboplatin. Cisplatin was associated with nephrotoxic effects, but K104 did not change the serum levels of BUN, creatinine and uric acid in vivo. These results suggest that K104 is a promising anticancer agent in view of its high efficacy against human solid cancer and lower toxicity in vivo.
BACKGROUND: The newly synthesized octahedral Pt(IV) complex series showed potent antitumor activities, both in vitro and in vivo. Carboplatin, possessing a soluble leaving ligand, is known to be less toxic than cisplatin. The synthesized K104 is a Pt(IV) complex with a malonato leaving group and seven-membered ring structure between the central platinum and amine carrier ligands. In this study, the histoculture drug response assay (HDRA) of K104 on humancancer tissues was investigated in vitro and nephrotoxicity was examined in vivo. MATERIALS AND METHODS:Cytotoxicity was tested in various cancer cell lines, and the HDRA of K104 was evaluated by MTT assay in vitro using colorectal and breast cancer tissues from patients. In order to compare the nephrotoxicity of K104 with cisplatin and carboplatin, blood serum levels of BUN, creatinine and uric acid in ICR mice were measured. RESULTS:K104 showed more effective anticancer activities than carboplatin in most cancer cell lines. In HDRA, K104 showed a 50.0-66.7% efficacy rate compared with 33.3% of cisplatin and 58.3% of carboplatin against colorectal cancerpatient tissues. In breast cancer tissues, K104 only showed an efficacy rate above 50%. The serum levels of BUN, creatinine and uric acid did not change after a single intraperitoneal administration of K104 (90 mg/kg) in ICR mice. CONCLUSION:K104 showed more effective anticancer activities than carboplatin. Cisplatin was associated with nephrotoxic effects, but K104 did not change the serum levels of BUN, creatinine and uric acid in vivo. These results suggest that K104 is a promising anticancer agent in view of its high efficacy against human solid cancer and lower toxicity in vivo.