Chemoprevention of benzo[a]pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil.

Abstract

Bioassay-directed fractionation of celery seed oil from the plant Apium graveolens (Umbelliferae) led to the isolation of five natural products, including d-limonene, p-mentha-2,8-dien-1-ol, p-mentha-8(9)-en-1,2-diol, 3-n-butyl phthalide, and sedanolide. Of these compounds p-mentha-2,8-dien-1-ol,3-n-butyl phthalide, and sedanolide exhibited high activities to induce the detoxifying enzyme glutathione S-transferase (GST) in the target tissues of female A/J mice. 3-n-Butyl phthalide and sedanolide (20 mg/dose every two days for a total of 3 doses) increased GST activity 4.5-5.9 and 3.2-5.2 times over the controls in the mouse liver and small intestinal mucosa, respectively. At the same dose, p-mentha-2,8-dien-1-ol induced GST activity about 3.7-fold above that of the controls. Thus, these compounds were further tested for their ability to inhibit benzo[a]pyrene- (BP) induced tumorigenesis in mice. After treatment with 3-n-butyl phthalide and sedanolide, the tumor incidence was reduced from 68% to 30% and 11%, respectively. About 67% and 83% reduction in tumor multiplicity was also observed with 3-n-butyl phthalide and sedanolide. p-Mentha-2,8-dien-1-ol produced only a small or no significant reduction of forestomach tumor formation. The data indicating that 3-n-butyl phthalide and sedanolide were both active in tumor inhibition and GST assays suggested a correlation between the inhibitory activity and the GST-inducing ability. The phthalides are known to determine the characteristic odor of celery. The results suggest that phthalides, as a class of bioactive natural products occurring in edible umbelliferous plants, may be effective chemopreventive agents.

• Authors: G Q Zheng, P M Kenney, J Zhang, L K Lam
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 19 Issue 1 Pg. 77-86 ( 1993) ISSN: 0163-5581 [Print] United States
• PMID: 8446516 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Phthalic Acids
• Plant Oils
• Benzo(a)pyrene
• Glutathione Transferase

Topics

• Animals
• Benzo(a)pyrene
• Drug Screening Assays, Antitumor
• Female
• Glutathione Transferase (drug effects, metabolism)
• Intestinal Mucosa (drug effects, enzymology)
• Liver (drug effects, enzymology)
• Mice
• Phthalic Acids (isolation & purification, therapeutic use)
• Plant Oils (therapeutic use)
• Stomach (drug effects, enzymology)
• Stomach Neoplasms (chemically induced, prevention & control)