Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice.
Bottom Line: Cancer chemotherapy is limited by the modest therapeutic index of most antineoplastic drugs.Beta-glucuronidase activated 9-aminocamptothecin glucuronide to produce similar cell killing as 9-aminocamptothecin or topotecan.The in vivo toxicity of 9-aminocamptothecin glucuronide in BALB/c mice was dose-, route-, sex- and age-dependent. 9-aminocamptothecin glucuronide was significantly less toxic to female than to male mice but the difference decreased with age. 9-aminocamptothecin glucuronide and 9-aminocamptothecin produced similar inhibition (approximately 80%) of LS174T human colorectal carcinoma tumours. 9-aminocamptothecin glucuronide cured a high percentage of CL1-5 human lung cancer xenografts with efficacy that was similar to or greater than 9-aminocamptothecin, irinotecan and topotecan.
Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, and ICTM, Center for Chemistry, Belgrade, Yugoslavia.Show MeSH
Related in: MedlinePlus
Mentions: The effect of age and sex on 9ACG toxicity was further examined by injecting 5, 10 and 20-week old male and female mice with 9AC or 9ACG. An i.v. injection of 50 mg kg−1 9ACG produced about 25% weight loss in 5-week old male mice (Figure 2AFigure 2
Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, and ICTM, Center for Chemistry, Belgrade, Yugoslavia.