Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase.
For the discovery of new cancer chemopreventive agents, we have studied the potential of plant extracts to inhibit phorbol ester-induced ornithine decarboxylase (ODC) activity in cell culture. Four active rotenoids were obtained from the African plant Mundulea sericea (Leguminosae). These isolates were highly potent when evaluated for inhibition of chemically induced preneoplastic lesions in mammary organ culture and inhibition of papillomas in the two-stage mouse skin model, and they appear to function by a unique mechanism at the level of ODC messenger RNA expression. Based on our findings, rotenoids can be regarded as promising new chemopreventive or anticancer agents.
Gerhäuser
C
C
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
Mar
W
W
Lee
S K
SK
Suh
N
N
Luo
Y
Y
Kosmeder
J
J
Luyengi
L
L
Fong
H H
HH
Kinghorn
A D
AD
Moriarty
R M
RM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018922:HL-60 Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011230:Precancerous Conditions / Q000517:prevention & control; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D012402:Rotenone; D015127:9,10-Dimethyl-1,2-benzanthracene; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate