Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells

Mostafa A. Borahay; Gokhan S. Kilic; Chrasekha Yallampalli; Russell R. Snyder; Gary D.V. Hankins; Ayman Al-Hendy; Darren Boehning

doi:10.1074/jbc.M114.583575

Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells

Mostafa A. Borahay, Gokhan S. Kilic, Chrasekha Yallampalli, Russell R. Snyder, Gary D.V. Hankins, Ayman Al-Hendy, Darren Boehning

Obstetrics & Gynecology

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

40 Scopus citations

Abstract

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltagegated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.

Original language	English (US)
Pages (from-to)	35075-35086
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	289
Issue number	51
DOIs	https://doi.org/10.1074/jbc.M114.583575
State	Published - Dec 19 2014

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1074/jbc.M114.583575

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title = "Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells",

abstract = "Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltagegated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.",

author = "Borahay, {Mostafa A.} and Kilic, {Gokhan S.} and Chrasekha Yallampalli and Snyder, {Russell R.} and Hankins, {Gary D.V.} and Ayman Al-Hendy and Darren Boehning",

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TY - JOUR

T1 - Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells

AU - Borahay, Mostafa A.

AU - Kilic, Gokhan S.

AU - Yallampalli, Chrasekha

AU - Snyder, Russell R.

AU - Hankins, Gary D.V.

AU - Al-Hendy, Ayman

AU - Boehning, Darren

PY - 2014/12/19

Y1 - 2014/12/19

N2 - Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltagegated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.

AB - Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltagegated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.

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Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells

Abstract

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