Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation.
We previously demonstrated that ursodeoxycholic acid (UDC) requires prolonged (≥5 h) preincubation to exhibit effective protection of colon cancer HCT116 cells from deoxycholic acid (DC)-induced apoptosis. Although UDC diminished DC-mediated caspase-9 activation, cytochrome c release from the mitoch...
| Publicado en: | Nutrition & Cancer Vol. 64; no. 4; pp. 617 - 627 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research Journal Article |
| Publicado: |
Taylor & Francis Ltd
May2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104564812&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104564812 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01635581 7MS jtl: Nutrition & Cancer issn: 01635581 maglogo: N pubinfo: dt: May2012 vid: 64 iid: 4 pid: 377 pub: Taylor & Francis Ltd place: Philadelphia, Pennsylvania artinfo: ui: 104564812 75063219 10.1080/01635581.2012.669876 NLM22497644 104564812 ppf: 617 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation. aug: au: Saeki, Tohru Yui, Satoko Hirai, Tadashi Fujii, Takami Okada, Sawami Kanamoto, Ryuhei affil: Laboratory of Molecular Nutrition, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Japan sug: subj: Colonic Neoplasms Therapy Bile Acids and Salts Therapeutic Use Cell Physiology Apoptosis Nutrition Cell Culture Techniques Biological Assay DNA Polymerase Chain Reaction Enzyme-Linked Immunosorbent Assay Data Analysis Densitometry RNA Physiology ab: We previously demonstrated that ursodeoxycholic acid (UDC) requires prolonged (≥5 h) preincubation to exhibit effective protection of colon cancer HCT116 cells from deoxycholic acid (DC)-induced apoptosis. Although UDC diminished DC-mediated caspase-9 activation, cytochrome c release from the mitochondria was not inhibited, indicating that UDC acts on the steps of caspase-9 activation. In the present study, therefore, we investigated the effects of UDC on the factors involved in caspase-9 activation. We found that UDC had no significant effect on the expression of antiapoptotic XIAP. Furthermore, UDC did not affect the expression or release of proapoptotic Smac/DIABLO, or the association of XIAP and Smac/DIABLO. In contrast, association of Apaf-1 and caspase-9 stimulated by 500 μM DC was inhibited by UDC pretreatment. Although UDC caused remarkable activation of Akt/PKB, phosphatidylinositol-3-kinase (PI3K) inhibitor did not significantly reduce UDC-mediated cytoprotection. Furthermore, phosphorylation of threonine residues on caspase-9 after UDC pretreatment could not be detected. UDC-mediated cytoprotection was independent of the MAPK pathway, and cyclic AMP (cAMP) analogue did not inhibit DC-induced apoptosis. Our results indicate that UDC protects colon cancer cells from apoptosis induced by hydrophobic bile acids, by inhibiting apoptosome formation independently of the survival signals mediated by the PI3K, MAPK, or cAMP pathways. pubtype: Academic Journal doctype: pictorial research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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