Taurocholic Acid Does Not Induce Apoptosis in HCT116 Cells Regardless of Its Intracellular Concentration

Yui, Satoko; Kanamoto, Ryuhei; Iwami, Kimikazu; Saeki, Tohru

doi:10.1271/bbb.60508

Cited by 2 publications

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References 16 publications

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“…In rat hepatocytes, glycochenodeoxycholic acid (GCDC) induces apoptosis via ligand-independent Fas oligomerization (1,2). In contrast, GCDC is not responsible for apoptosis in human colon cancer-derived HCT116 cells (3). In hepatocytes, apoptosis by the hydrophobic secondary bile acid, deoxycholic acid (DC), requires expression and aggregation of death receptor 5 (DR5), also designated as tumor necrosis factor-related, apoptosisinducing ligand-receptor 2 (TRAIL-R2) (4).…”

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation

Saeki

Yui

Hirai

et al. 2012

Nutrition and Cancer

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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.

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Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation

Saeki

Yui

Hirai

et al. 2012

Nutrition and Cancer

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Biphasic Regulation of Cell Death and Survival by Hydrophobic Bile Acids in HCT116 Cells

Yui

Kanamoto

Saeki

2009

Nutrition and Cancer

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A secondary bile acid, namely, deoxycholic acid (DCA), has been known to promote colon tumors; on the other hand, it also induces apoptosis in several human colon cancer cell lines. A hydrophobic primary bile acid, namely, chenodeoxycholic acid (CDCA), exhibits a similar property of apoptosis induction; DCA and CDCA also trigger some specific intracellular signal pathways in the human colon cancer cell line HCT116. In this article, we report that hydrophobic bile acids induce different cellular responses depending on their concentration, that is, a sublethal concentration of hydrophobic bile acids can suppress the apoptosis induced by a higher concentration of DCA. Pretreatment with DCA or CDCA at a concentration of < or = 200 microM for 8 h suppressed the apoptosis induced by 500 microM DCA in HCT116 cells. Under this condition, the association of caspase-9 and Apaf-1 and subsequent activation of caspase-9 were inhibited, but the release of cytochrome c from the mitochondria was not. At 200 microM, DCA and CDCA induced the phosphorylation of Akt and ERK1/2, although these phosphorylations do not appear to be indispensable for the cytoprotection. It is interpreted that prolonged exposure to sublethal concentrations of hydrophobic bile acids induces resistance to apoptosis, leading to promotion of colorectal tumorigenesis.

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Taurocholic Acid Does Not Induce Apoptosis in HCT116 Cells Regardless of Its Intracellular Concentration

Cited by 2 publications

References 16 publications

Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation

Ursodeoxycholic Acid Protects Colon Cancer HCT116 Cells From Deoxycholic Acid-Induced Apoptosis by Inhibiting Apoptosome Formation

Biphasic Regulation of Cell Death and Survival by Hydrophobic Bile Acids in HCT116 Cells

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