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Cancer Prevention Research
Cancer Prevention Research
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Research Article

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, M. Gerard O'Sullivan, Mesfin Negia, Timothy E. Hanson, Pramod Upadhyaya, Peter P. Ruvolo, Stephen S. Hecht and Chengguo Xing
Thomas E. Johnson
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Fekadu Kassie
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M. Gerard O'Sullivan
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Mesfin Negia
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Timothy E. Hanson
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Pramod Upadhyaya
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Peter P. Ruvolo
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Stephen S. Hecht
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Chengguo Xing
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DOI: 10.1158/1940-6207.CAPR-08-0027 Published November 2008
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Abstract

Lung cancer is the leading cause of cancer death, and chemoprevention is a potential strategy to help control this disease. Epidemiologic survey indicates that kava may be chemopreventive for lung cancer, 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 lung tumorigenesis 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 lung tumor multiplicity by 56%. Kava also reduced lung tumor multiplicity by 47% when administered concurrently with NNK and B[a]P for 8 weeks. Perhaps most importantly, kava reduced lung tumor 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 lung tumors, 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.

Keywords
  • kava
  • chemoprevention
  • lung
  • tumorigenesis
  • B[a]P
  • NNK
  • hepatotoxicity
  • proliferation
  • apoptosis
  • NF-êB
  • Received February 8, 2008.
  • Revision received March 12, 2008.
  • Accepted March 20, 2008.
  • ©2008 American Association for Cancer Research.
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Cancer Prevention Research: 1 (6)
November 2008
Volume 1, Issue 6
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  • 2008 Frontiers in Cancer Prevention Research Abstracts: Supplement to Vol. 1, Issue 7

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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, M. Gerard O'Sullivan, Mesfin Negia, Timothy E. Hanson, Pramod Upadhyaya, Peter P. Ruvolo, Stephen S. Hecht and Chengguo Xing
Cancer Prev Res November 1 2008 (1) (6) 430-438; DOI: 10.1158/1940-6207.CAPR-08-0027

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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, M. Gerard O'Sullivan, Mesfin Negia, Timothy E. Hanson, Pramod Upadhyaya, Peter P. Ruvolo, Stephen S. Hecht and Chengguo Xing
Cancer Prev Res November 1 2008 (1) (6) 430-438; DOI: 10.1158/1940-6207.CAPR-08-0027
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