A novel camptothecin analog with enhanced antitumor activity.
BACKGROUND
The use of camptothecin (CPT) derivatives is limited by severe toxicity associated with the instability of their chemical structure. We have developed a stable CPT derivative (CPT417) and have investigated its biological activity in comparison to the currently used CPT analogs.


METHODS
The anticancer effects of CPT417 were assessed in vitro, with glioblastoma and colon cancer cell lines, and in vivo with mice bearing mammary adenocarcinoma tumors implanted subcutaneously in the flank. Cytotoxicity was assessed using vital dye exclusion, timelapse microscopy and colony formation.


RESULTS
CPT417 and topotecan inhibited glioblastoma cell growth at comparable levels and both compounds inhibited clonogenicity of colon cancer cells more effectively than irinotecan. CPT417 showed a much greater inhibition of mammary tumor growth compared to topotecan, both by intraperitoneal and oral administration.


CONCLUSIONS
CPT417 shows dramatically reduced toxicity and an enhanced antitumor activity compared to topotecan.
Yount
Garret
G
California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
Yang
Yang
Y
Wong
Brian
B
Wang
Hui-Juan
HJ
Yang
Li-Xi
LX
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D019772:Topotecan / Q000494:pharmacology
D000970:Antineoplastic Agents; C524373:CPT417; D019772:Topotecan; D002166:Camptothecin