Inhibition of benzo[a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil.
Glutathione S-transferase (GST) assay-guided fractionation of parsley leaf oil from the edible plant Petroselinum sativum Hoffm. (Umbelliferae) led to the isolation of myristicin. Myristicin showed high activity as an inducer of the detoxifying enzyme GST in the liver and small intestinal mucosa of female A/J mice. Reduction of myristicin yielded dihydromyristicin that retained the GST-inducing activity. Myristicin and dihydromyristicin were tested for their capacity to inhibit benzo[a]pyrene (B[a]P)-induced tumor formation in female A/J mice. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin. Dihydromyristicin produced small or insignificant reduction of lung tumor formation. In the forestomach, myristicin showed a 31% inhibition of tumor formation; while dihydromyristicin exhibited a 27% inhibition. Comparison of the structures and activities indicated that the saturation of the isolated double bond in myristicin resulted in a significant decrease in the inhibitory activity against B[a]P-induced tumorigenesis. The present results showed that myristicin, an active inducer of GST activity, is an effective inhibitor of B[a]P-induced tumorigenesis in mice. Stimulation of GST activity by myristicin could be a major mechanism for its inhibition of B[a]P or other carcinogens that may be detoxified in the same manner. As a culinary herb parsley is regularly consumed by humans. Parsley leaf oil is also used extensively for garnishing and seasoning. The results of this study indicate that as a major volatile aroma constituent of parsley myristicin may be an effective cancer chemopreventive agent.
Zheng
G Q
GQ
LKT Laboratories, Inc., Minneapolis, MN 55413.
Kenney
P M
PM
Zhang
J
J
Lam
L K
LK
D000081248:Allylbenzene Derivatives; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors*; D001593:Benzyl Compounds; D004148:Dioxolanes / Q000627:therapeutic use*; D004790:Enzyme Induction; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D010936:Plant Extracts / Q000627:therapeutic use*; D011748:Pyrogallol / Q000031:analogs & derivatives
D000081248:Allylbenzene Derivatives; D016588:Anticarcinogenic Agents; D001593:Benzyl Compounds; D004148:Dioxolanes; D010936:Plant Extracts; D011748:Pyrogallol; C005246:myristicin; D001564:Benzo(a)pyrene; C077582:dihydromyristicin; D005982:Glutathione Transferase