Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary flavonoids have been shown to exert specific cytotoxicity towards some cancer cells, but the precise molecular mechanisms are still not completely understood. In our study, cytotoxic effects of structurally related flavones and flavonols on a human oesophageal adenocarcinoma cell line (OE33) were compared, and the molecular mechanisms responsible for their cytotoxic effects were explored. The results of MTT assay showed that flavones (luteolin, apigenin, chrysin) and flavonols (quercetin, kaempferol, myricetin) were all able to induce cytotoxicity in OE33 cells in a dose- and time-dependent manner, and the cytotoxic potency of these compounds was in the order of quercetin>luteolin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA fragmentation analysis indicated that the cytotoxicity induced by flavones and flavonols was mediated by G2/M cell cycle arrest and apoptosis. Furthermore, the expression of genes related to cell cycle arrest and apoptosis was assessed by oligonucleotide microarray, real-time RT-PCR and Western blot. It was found that the treatment of OE33 cells with flavones and flavonols caused G2/M arrest through up-regulation of GADD45beta and 14-3-3sigma and down-regulation of cyclin B1 at the mRNA and protein levels, and induced p53-independent mitochondrial-mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The results of western blot analysis further showed that increases of p63 and p73 protein translation or stability might be contribute to the regulation of GADD45beta, 14-3-3sigma, cyclin B1 and PIG3.
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PMID:Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. 1833 76

In this study, cytotoxic effects of structurally related flavones and flavonols on a human esophageal squamous cell carcinoma cell line (KYSE-510) were determined, and the molecular mechanisms responsible for their cytotoxic effects were studied. The results of MTT assay showed that flavones (luteolin, apigenin, chrysin) and flavonols (quercetin, kaempferol, myricetin) were able to induce cytotoxicity in KYSE-510 cells in a dose- and time-dependent manner, and the cytotoxic potency of these compounds was in the order of: luteolin>quercetin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA fragmentation analysis indicated that the cytotoxicity induced by flavones and flavonols was mediated by G(2)/M cell cycle arrest and apoptosis. Furthermore, the expression of genes related to cell cycle arrest and apoptosis was assessed by oligonucleotide microarray, real-time RT-PCR and Western blot. It was shown that the treatment of KYSE-510 cells with these compounds caused G(2)/M arrest through up-regulation of p21(waf1) and down-regulation of cyclin B1 at the mRNA and protein levels, and induced p53-independent mitochondrial-mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The results of western blot analysis further showed that increases of p63 and p73 protein translation or stability might be contributed to the regulation of p21(waf1), cyclin B1 and PIG3.
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PMID:Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. 1939 94

Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to play a role in cancer development and progression. However, the role of HPIP in colorectal cancer (CRC) is unknown. Here, we report that HPIP is overexpressed in most of CRC patients and predicts poor clinical outcome in CRC. HPIP promotes CRC cell proliferation via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. HPIP inhibits CRC cell apoptosis accompanied by the decreased levels of BAX and PIG3, the inducers of apoptosis, and the increased level of the apoptosis inhibitor BCL2. HPIP blocks caspase-3-mediated cleavage of PARP, an important apoptosis marker. HPIP promotes CRC cell migration and invasion, and regulates epithelial-mesenchymal transition (EMT), which plays a critical role in cancer cell migration and invasion. Activation of MAPK/ERK1/2 and PI3k/AKT pathways is required for HPIP modulation of CRC cell proliferation, migration and EMT. Moreover, HPIP knockdown suppresses colorectal tumor growth in nude mice. These data highlight the important role of HPIP in CRC cell proliferation and progression and suggest that HPIP may be a useful target for CRC therapy.
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PMID:HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion. 2580 Jul 93