Antitumor activity and mechanism of action of the marine compound girodazole.
Girodazole, a new marine compound has been isolated from the sponge Pseudaxinyssa cantharella. Girodazole is active in vivo on several murine grafted tumors including leukemias (P388, L1210, i.p./i.p.) and solid tumors (MA 16/C mammary adenocarcinoma, M5076 histiocytosarcoma, s.c./i.v.). In addition, girodazole has identical cytotoxic properties in vitro on P388 and P388/DOX cells and retains antitumor activity in vivo on P388/DOX. Girodazole has a unique chemical structure different from those of known anticancer agents and of new compounds undergoing clinical trials. Biochemical studies indicate that girodazole inhibits protein synthesis during the elongation/termination steps. Toxicological studies have been done in mice and in dogs and did not reveal any major toxic effect which could preclude administration in patients. Girodazole is now undergoing phase I clinical studies.
Lavelle
F
F
Département de Biologie, Centre de Recherches de Vitry-Alfortville, Vitry sur Seine, France.
Zerial
A
A
Fizames
C
C
Rabault
B
B
Curaudeau
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011817:Rabbits; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007093:Imidazoles; D009363:Neoplasm Proteins; D011412:Propanolamines; D012334:RNA, Neoplasm; C072834:girodazole