Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent.

Abstract

A novel anti-tumor agent, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103), effectively inhibits both topoisomerase I and II activities. To enhance anti-tumor efficacy and to reduce the side effects of the agent, liposomalization of TAS-103 was performed. TAS-103 was effectively entrapped in liposomes by a remote-loading method, and was stable at 4 degrees C and in the presence of 50% serum. To evaluate the anti-tumor efficacy of liposomal TAS-103, the growth inhibition against Lewis lung carcinoma cells in vitro and the therapeutic efficacy against solid tumor-bearing mice in vivo were examined. Liposomal TAS-103 showed strong cytotoxic effect against Lewis lung carcinoma cells in a dose dependent manner and effectively suppressed solid tumor growth accompanying longer survival time of tumor-bearing mice in comparison with the mice treated with free TAS-103. These results suggest that liposomal TAS-103 is useful for cancer therapy.

• Authors: Kosuke Shimizu, Miki Takada, Tomohiro Asai, Koichi Kuromi, Kazuhiko Baba, Naoto Oku
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 25 Issue 10 Pg. 1385-7 (Oct 2002) ISSN: 0918-6158 [Print] Japan
• PMID: 12392102 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Aminoquinolines
• Antineoplastic Agents
• Indenes
• Liposomes
• Topoisomerase II Inhibitors
• 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one

Topics

• Aminoquinolines (administration & dosage)
• Animals
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Lewis Lung (drug therapy, enzymology)
• Dose-Response Relationship, Drug
• Indenes (administration & dosage)
• Liposomes
• Male
• Mice
• Mice, Inbred C57BL
• Survival Rate
• Topoisomerase II Inhibitors
• Xenograft Model Antitumor Assays (methods)