Abstract:
:Tangeretin, a major phytochemicals in tangerine peels--an important Chinese herb, has been found to have anti-carcinogenic properties. To improve bioavailability and increase potency of tangeretin, its derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone (5-AcTMF), has been synthesized and shown potent inhibition of proliferation activity against human breast and leukemia cancer cell lines. In this study, we have further investigated the anticancer effects of 5-AcTMF on CL1-5 non-small cell lung cancer cells (NSCLC) both in vitro and in vivo and demonstrated that 5-AcTMF effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with cdc2 and CDC25c and increased in the apoptotic cells associated with caspase activation, down regulation of Bcl-2, XIAP and Survivn, inducing release of cytochrome c into the cytosol and disruption of mitochondrial membrane potential. We also found that 5-AcTMF treatment of CL1-5 activated autophagy, indicated by triggered autophagosome formation and increased LC3-II levels and formation of LC3 puncta. Moreover, we also found that 5-AcTMF lowered phophoatidylinositol 3-kinase/AKT/mTOR signaling pathway. Over-expression of AKT by AKT cDNA transfection decreased 5-AcTMF mediated apoptosis and autophagy, supporting the induction of apoptosis and autophagy by inhibition of AKT pathway. In an animal study, 5-AcTMF effectively delayed tumor growth in a nude mouse model of CL1-5 xenografts without observed adverse effect. Immunohistochemistry Analysis indicated that 5-AcTMF induced CL1-5 cell apoptosis and autophagy in vivo. Taken together, these data demonstrate that 5-AcTMF is a novel small molecule agent that can inhibit NSCLC cell proliferation, and induce G(2)/M phase arrest and via the mitochondrial apoptotic pathway and autophagy.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Li YR,Li S,Ho CT,Chang YH,Tan KT,Chung TW,Wang BY,Chen YK,Lin CCdoi
10.1080/15384047.2015.1108491subject
Has Abstractpub_date
2016-01-01 00:00:00pages
48-64issue
1eissn
1538-4047issn
1555-8576journal_volume
17pub_type
杂志文章abstract::Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer dev...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20840
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:
更新日期:2003-07-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.8.14906
更新日期:2011-04-15 00:00:00
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
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更新日期:2009-05-01 00:00:00
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journal_title:Cancer biology & therapy
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