Chemopreventive effect of kava on 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone plus benzo[a]pyrene-induced lung tumorigenesis in A/J mice

Thomas E. Johnson, Fekadu Kassie, Gerard O'Sullivan, Mesfin Negia, Timothy E. Hanson, Pramod Upadhyaya, Peter P. Ruvolo, Stephen S Hecht, Chengguo Xing

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31 Scopus citations

Abstract

Lung cancer is the leadingca use of cancer death, and chemoprevention is a potential strategy to help control this disease. Epidemiologic survey indicates that kava may be chemopreventive for lungcancer, but there is a concern about its potential hepatotoxicity. In this study, we evaluated whether oral kava could prevent 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (B[a]P)-induced lungt umorigenesis in A/J mice. We also studied the effect of kava to liver. At a dose of 10 mg/g diet, 30-week kava treatment (8 weeks concurrent with NNK and B[a]P treatment followed by 22 weeks post-carcinogen treatment) effectively reduced lungtumor multiplicity by 56%. Kava also reduced lungtumor multiplicity by 47% when administered concurrently with NNK and B[a]P for 8 weeks. Perhaps most importantly, kava reduced lungt umor multiplicity by 49% when administered after the final NNK and B[a]P treatment. These results show for the first time the chemopreventive potential of kava against lung tumorigenesis. Mechanistically, kava inhibited proliferation and enhanced apoptosis in lungtumors, as shown by a reduction in proliferating cell nuclear antigen (PCNA), an increase in caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP). Kava treatment also inhibited the activation of nuclear factor κBNF-κB, a potential upstream mechanism of kava chemoprevention. Although not rigorously evaluated in this study, our preliminary data were not suggestive of hepatotoxicity. Based on these results, further studies are warranted to explore the chemopreventive potential and safety of kava.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalCancer Prevention Research
Volume1
Issue number6
DOIs
StatePublished - Nov 2008

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