human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: BACKGROUND Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables . We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest . The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor ( IGF-IR ) signaling pathway in HT-29 cells . METHODS In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway , cells were cultured with or without 60 Î¼mol/L luteolin and/or 10 nmol/L IGF-I . Cell proliferation , DNA synthesis , and IGF-IR mRNA levels were evaluated by a cell viability assay , [ 3H]thymidine incorporation assays , and real-time polymerase chain reaction , respectively . Western blot analyses , immunoprecipitation , and in vitro kinase assays were conducted to evaluate the secretion of IGF-II , the protein expression and activation of IGF-IR , and the association of the p85 subunit of phophatidylinositol-3 kinase ( PI3K ) with IGF-IR , the phosphorylation of Akt and extracellular signal-regulated kinase ( ERK)1/2 , and cell division cycle 25c ( CDC25c ) , and PI3K activity . RESULTS Luteolin ( 0 - 60 Î¼mol/L ) dose-dependently reduced the IGF-II secretion of HT-29 cells . IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition . Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts . Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR . Additionally , luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt , ERK1/2 , and CDC25c in the presence and absence of IGF-I stimulation . CONCLUSIONS The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells ; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest .
    OUTPUT:

agent
sustaining proliferative signaling;resisting cell death
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: BACKGROUND Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables . We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest . The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor ( IGF-IR ) signaling pathway in HT-29 cells . METHODS In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway , cells were cultured with or without 60 Î¼mol/L luteolin and/or 10 nmol/L IGF-I . Cell proliferation , DNA synthesis , and IGF-IR mRNA levels were evaluated by a cell viability assay , [ 3H]thymidine incorporation assays , and real-time polymerase chain reaction , respectively . Western blot analyses , immunoprecipitation , and in vitro kinase assays were conducted to evaluate the secretion of IGF-II , the protein expression and activation of IGF-IR , and the association of the p85 subunit of phophatidylinositol-3 kinase ( PI3K ) with IGF-IR , the phosphorylation of Akt and extracellular signal-regulated kinase ( ERK)1/2 , and cell division cycle 25c ( CDC25c ) , and PI3K activity . RESULTS Luteolin ( 0 - 60 Î¼mol/L ) dose-dependently reduced the IGF-II secretion of HT-29 cells . IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition . Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts . Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR . Additionally , luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt , ERK1/2 , and CDC25c in the presence and absence of IGF-I stimulation . CONCLUSIONS The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells ; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest .
    OUTPUT:
