Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo.
A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula diversivittata were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All of the tested compounds were active against EBV-EA activation. Among these compounds diversin (IC(50): 7.7) exhibited the strongest inhibitory effect and was selected to examine its effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited papilloma formation up to week 7 and the percentage of papilloma bearers was approximately 93.3% at week 20. The average number of papillomas formed per mouse was only 5.5 even at week 20. The results of the present investigation indicated that diversin might be valuable as a potent cancer chemopreventive agent and its potency was comparable with those of curcumin and quercetin, two well-known cancer chemopreventive agents.
Iranshahi
M
M
Department of Pharmacognosy, Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, (MUMS), P.O. Box: 91775-1365, Mashhad, Iran. Iranshahim@mums.ac.ir
Sahebkar
A
A
Hosseini
S T
ST
Takasaki
M
M
Konoshima
T
T
Tokuda
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002273:Carcinogens; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005309:Ferula / Q000737:chemistry*; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D039821:Monoterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D010212:Papilloma / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate
D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D003374:Coumarins; C033305:Epstein-Barr virus early antigen; D007783:Lactones; D039821:Monoterpenes; D010936:Plant Extracts; D012717:Sesquiterpenes; C551724:diversin; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate