Galbanic acid, a cytotoxic sesquiterpene from the gum resin of Ferula asafoetida, blocks protein farnesyltransferase.
Farnesylation of the activated RAS oncogene product by protein farnesyltransferase (FTase) is a critical step for its oncogenic function. Bioassay-guided purification of Ferula asafoetida (Umbelliferae) extract led to the isolation of the coumarin-derived sesquiterpene galbanic acid (1) as an active principal for FTase inhibitory activity, together with the four structurally related sesquiterpenes karatavicinol (2), umbelliprenin (3), farnesiferol B (4), and farnesiferol C (5). The 50 % inhibitory concentration (IC (50)) of 1 against FTase in an enzyme-based assay was calculated as 2.5 µM. Compound 1 also demonstrated potent inhibition of the proliferation of oncogenic RAS-transformed NIH3T3/Hras-F in a dose-dependent manner. The IC (50) value of 1 on the proliferation of oncogenic RAS-transformed NIH3T3/Hras-F cells was calculated as 16.2 µM, whereas its IC (50) value on control vector-transfected normal RAS-containing NIH3T3/ZIPneo cells was 58.5 µM.
Cha
Mi-Ran
MR
Korea Research Institute of Chemical Technology, Daejeon, Korea.
Choi
Yeon Hee
YH
Choi
Chun Whan
CW
Kim
Young Sup
YS
Kim
Young-Kyoon
YK
Ryu
Shi Yong
SY
Kim
Young Ho
YH
Choi
Sang Un
SU
D000818:Animals; D001921:Brain / Q000201:enzymology; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D005309:Ferula / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D041681:NIH 3T3 Cells; D054876:Prenylation / Q000187:drug effects; D051381:Rats
D003374:Coumarins; D054697:Cytostatic Agents; C048972:galbanic acid; D051231:Farnesyltranstransferase