Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice.

Abstract

Lung cancer is the most deadly malignancy in the US. Chemoprevention is potentially a complementary approach to smoking cessation for lung cancer control. Recently, we reported that a commercially available form of kava extract significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg per gram diet. In the present study, we examined the dose-dependent lung tumor inhibitory activities of kava and investigated potential active constituent(s). Mice treated with carcinogen alone contained 12.1±5.8 lung adenomas per mouse 22 weeks after final carcinogen administration. Mice that were fed diets containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4±3.5, 6.6±3.5, 4.3±2.4, and 3.8±2.3 lung adenomas per mouse, respectively. This corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which were all statistically significant (p < 0.05). Analyses of lung adenoma tissues derived from kava-treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based components from kava, demonstrated greatly reduced chemopreventive efficacies even at concentrations much higher than their natural abundance, suggesting that they alone were unlikely to be responsible for kava's chemopreventive activity. Kava at all dosages and treatment regimens did not induce detectable adverse effects, particularly with respect to liver. Specifically, kava treatment showed no effect on liver integrity indicator enzymes or liver weight, indicating that kava may be potentially safe for long-term chemopreventive application.

• Authors: Thomas E Johnson, David Hermanson, Lei Wang, Fekadu Kassie, Pramod Upadhyaya, Michael G O'Sullivan, Stephen S Hecht, Junxuan Lu, Chengguo Xing
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 39 Issue 4 Pg. 727-42 ( 2011) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 21721153 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Carcinogens
• Nitrosamines
• Plant Extracts
• Benzo(a)pyrene
• Chalcone
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Topics

• Adenocarcinoma (chemically induced, prevention & control)
• Adenocarcinoma of Lung
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Benzo(a)pyrene
• Carcinogens
• Cell Death (drug effects)
• Cell Proliferation (drug effects)
• Chalcone (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Female
• Kava (chemistry)
• Liver (drug effects)
• Lung Neoplasms (chemically induced, prevention & control)
• Mice
• Mice, Inbred Strains
• Nitrosamines
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)