Indocarbazostatin and indocarbazostatin B, novel inhibitors of NGF-induced neuronal differentiation in PC12 cells. I. Screening, taxonomy, fermentation and biological activities.
During the course of our screening for modulators of signal transduction of mammalian cells, we discovered two novel indolocarbazole antibiotics, indocarbazostatin and indocabazostatin B, from a culture broth of a Streptomyces sp. as inhibitors of NGF-induced neuronal differentiation in rat pheochromocytoma PC12 cells. Indocarbazostatin and indocarbazostatin B inhibited NGF-induced neurite outgrowth from PC12 cells at 6 nM and 24 nM, respectively, whereas K-252a inhibited at 200 nM under our assay conditions.
Matsuura
Nobuyasu
N
Biotechnology Research Center, Toyama Prefectural University, Kosugi, Japan.
Tamehiro
Norimasa
N
Andoh
Tsutomu
T
Kawashima
Akira
A
Ubukata
Makoto
M
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D003470:Culture Media; D005285:Fermentation; D006131:Growth Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D013302:Streptomyces / Q000145:classification / Q000254:growth & development / Q000378:metabolism*
D002227:Carbazoles; D003470:Culture Media; D006131:Growth Inhibitors; D007211:Indoles; C402701:indocarbazostatin; C458887:indocarbazostatin B; D020932:Nerve Growth Factor