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Article: Anticancer efficacy of 5F in NNK-induced lung cancer development of A/J mice and human lung cancer cells

TitleAnticancer efficacy of 5F in NNK-induced lung cancer development of A/J mice and human lung cancer cells
Authors
Issue Date2010
PublisherSpringer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109
Citation
Journal of Molecular Medicine, 2010, v. 88 n. 12, p. 1265-1276 How to Cite?
AbstractThe mechanism responsible for the apoptotic effect induced by ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is not fully understood and its in vivo effect has not been tested. In this study, the effect and mechanism of 5F was investigated in cigarette smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-butanone (NNK)-induced mouse lung tumor model and in cultured lung cancer cells NCI-H23 and CRL-2066. 5F were given to mice after they were treated with NNK for 18 weeks. The effect of 5F on the lung tumor formation was examined, and its side effect was monitored. Cell proliferation and apoptosis were determined through expression of PCNA, Bcl-2, Bax, and TUNEL assay in in vivo animal model. 5F significantly inhibited the NNK-induced lung tumors by inducing apoptosis and suppressing cell proliferation in vivo with minimal side effects. Cell culture experiments showed that 5F translocated Bax into the mitochondria, downregulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol, and translocated AIF from the mitochondria to the nucleus, which leading to G2-M cell cycle arrest and cell apoptosis. 5F also activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. In addition to ERK1/2, 5F activated Akt. The inhibition of Akt further facilitated the apoptosis induced, suggesting that Akt activation was anti-apoptotic rather than pro-apoptotic. Collectively, 5F is effective against lung cancer in vivo with minimal side effects. It induces apoptosis in lung cancer through the mitochondrial-mediated pathway, in which the activation of ERK is critical. © Springer-Verlag 2010.
Persistent Identifierhttp://hdl.handle.net/10722/192683
ISSN
2015 Impact Factor: 4.855
2015 SCImago Journal Rankings: 2.165

 

DC FieldValueLanguage
dc.contributor.authorLi, M-Yen_US
dc.contributor.authorLeung, Jen_US
dc.contributor.authorKong, AWYen_US
dc.contributor.authorLiang, NCen_US
dc.contributor.authorWu, Ken_US
dc.contributor.authorHsin, MKYen_US
dc.contributor.authorDeng, YFen_US
dc.contributor.authorGong, Xen_US
dc.contributor.authorLv, Yen_US
dc.contributor.authorMok, TSKen_US
dc.contributor.authorUnderwood, MJen_US
dc.contributor.authorChen, GGen_US
dc.date.accessioned2013-11-20T04:55:16Z-
dc.date.available2013-11-20T04:55:16Z-
dc.date.issued2010en_US
dc.identifier.citationJournal of Molecular Medicine, 2010, v. 88 n. 12, p. 1265-1276en_US
dc.identifier.issn0946-2716en_US
dc.identifier.urihttp://hdl.handle.net/10722/192683-
dc.description.abstractThe mechanism responsible for the apoptotic effect induced by ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is not fully understood and its in vivo effect has not been tested. In this study, the effect and mechanism of 5F was investigated in cigarette smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-butanone (NNK)-induced mouse lung tumor model and in cultured lung cancer cells NCI-H23 and CRL-2066. 5F were given to mice after they were treated with NNK for 18 weeks. The effect of 5F on the lung tumor formation was examined, and its side effect was monitored. Cell proliferation and apoptosis were determined through expression of PCNA, Bcl-2, Bax, and TUNEL assay in in vivo animal model. 5F significantly inhibited the NNK-induced lung tumors by inducing apoptosis and suppressing cell proliferation in vivo with minimal side effects. Cell culture experiments showed that 5F translocated Bax into the mitochondria, downregulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol, and translocated AIF from the mitochondria to the nucleus, which leading to G2-M cell cycle arrest and cell apoptosis. 5F also activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. In addition to ERK1/2, 5F activated Akt. The inhibition of Akt further facilitated the apoptosis induced, suggesting that Akt activation was anti-apoptotic rather than pro-apoptotic. Collectively, 5F is effective against lung cancer in vivo with minimal side effects. It induces apoptosis in lung cancer through the mitochondrial-mediated pathway, in which the activation of ERK is critical. © Springer-Verlag 2010.en_US
dc.languageengen_US
dc.publisherSpringer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109-
dc.relation.ispartofJournal of Molecular Medicineen_US
dc.titleAnticancer efficacy of 5F in NNK-induced lung cancer development of A/J mice and human lung cancer cellsen_US
dc.typeArticleen_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00109-010-0676-4en_US
dc.identifier.pmid20830463-
dc.identifier.scopuseid_2-s2.0-78651301750en_US
dc.identifier.volume88en_US
dc.identifier.issue12en_US
dc.identifier.spage1265en_US
dc.identifier.epage1276en_US

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