Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C

Janna M. Larue; Elias D. Stratagoules; Jesse D. Martinez

doi:10.1016/S0304-3835(99)00439-5

Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C

Janna M. Larue, Elias D. Stratagoules, Jesse D. Martinez

Cellular and Molecular Medicine

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original language	English (US)
Pages (from-to)	107-113
Number of pages	7
Journal	Cancer Letters
Volume	152
Issue number	1
DOIs	https://doi.org/10.1016/S0304-3835(99)00439-5
State	Published - Apr 28 2000

Keywords

Apoptosis
Bile acids
Caspases
Necrosis
Protein kinase C

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/S0304-3835(99)00439-5

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title = "Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C",

abstract = "We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid. Copyright (C) 2000 Elsevier Science Ireland Ltd.",

keywords = "Apoptosis, Bile acids, Caspases, Necrosis, Protein kinase C",

author = "Larue, {Janna M.} and Stratagoules, {Elias D.} and Martinez, {Jesse D.}",

note = "Funding Information: We would like to thank Roger Miesfeld for providing us with the PSFFU neo plasmid. This work was supported by NIH grant CA72008. E.D. Stratagoules and J.M. LaRue were supported, in part, by Howard Hughes Medical Institute Grant 71195-521303.",

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doi = "10.1016/S0304-3835(99)00439-5",

language = "English (US)",

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T1 - Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C

AU - Larue, Janna M.

AU - Stratagoules, Elias D.

AU - Martinez, Jesse D.

N1 - Funding Information: We would like to thank Roger Miesfeld for providing us with the PSFFU neo plasmid. This work was supported by NIH grant CA72008. E.D. Stratagoules and J.M. LaRue were supported, in part, by Howard Hughes Medical Institute Grant 71195-521303.

PY - 2000/4/28

Y1 - 2000/4/28

N2 - We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid. Copyright (C) 2000 Elsevier Science Ireland Ltd.

AB - We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid. Copyright (C) 2000 Elsevier Science Ireland Ltd.

KW - Apoptosis

KW - Bile acids

KW - Caspases

KW - Necrosis

KW - Protein kinase C

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AN - SCOPUS:0034724964

SN - 0304-3835

VL - 152

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JO - Cancer Letters

JF - Cancer Letters

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ER -

Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C

Abstract

Keywords

ASJC Scopus subject areas

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