[Growth inhibition of human pancreatic cancer by farnesyl transferase inhibitor].
Ras is one of the key components in the signal transduction for cell growth. For acquisition of biological activity, Ras protein is required to bind to the inside of the plasma membrane after post-translational farnesylation. Manumycin, a competitive farnesyl transferase inhibitor, inhibits the growth of human pancreatic cancer cells (SUIT-2, MIAPaCa-2, AsPC-1, BxPC-3) in a dose dependent manner. The inhibitory concentration (IC50) of cell lines with a mutant K-ras gene (SUIT-2, MIAPaCa-2, AsPC-1) was lower than that of BxPC-3 with a wild-type. A high concentration of manumycin induced apoptosis, which is related to the inhibition of cell growth. Inhibition of Ras activity might be a new anti-cancer therapy in pancreatic cancer in which Ras plays a role.
Kainuma
O
O
Second Dept. of Surgery, Chiba University School of Medicine, Japan.
Asano
T
T
Hasegawa
M
M
Isono
K
K
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D051231:Farnesyltranstransferase; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017354:Point Mutation; D011090:Polyenes / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D014166:Transferases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000187:drug effects
D000900:Anti-Bacterial Agents; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D018631:ras Proteins; C054474:manumycin