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  • Title: Participation of Omi Htra2 serine-protease activity in the apoptosis induced by cisplatin on SW480 colon cancer cells.
    Author: Pruefer FG, Lizarraga F, Maldonado V, Melendez-Zajgla J.
    Journal: J Chemother; 2008 Jun; 20(3):348-54. PubMed ID: 18606591.
    Abstract:
    Apoptosis is triggered by two interconnected pathways, extrinsic and intrinsic. The intrinsic pathway is activated by genomic stress promoting mitochondrial release of apoptotic proteins. One of these proteins is Omi/Htra2, a serine protease which inactivates Inhibitor of Apoptosis Proteins (IAPs). In the present work, we assessed the participation of Omi/Htra2 in the cell death induced by the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP) in SW480 colon cancer cells. CDDP and 5-FU induced apoptosis mediated by the intrinsic pathway in colon cancer cells, as demonstrated by morphological analyses, mitochondrial cytochrome c release and cleavage of caspase 3. Omi/Htra2 was also released from mitochondria of cells exposed to these drugs, as demonstrated by immunofluorescence and western blot assays of subcellular fractions. Exposure of cells to the Omi/Htra2 serine protease inhibitor UCF-101 prevented death p<0.0001 and partially suppressed reproductive cell death of cells exposed to cisplatin p<0.05, but not to 5-FU p=0.49. From these experiments we show that Omi/Htra2 serine protease activity participates in the cell death induced by CDDP but not of 5-FU in colon cancer cells.
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