Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)35075-35086
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number51
DOIs
StatePublished - Dec 19 2014

Fingerprint

Simvastatin
Leiomyoma
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Apoptosis
Calcium
Calcium Channels
Hypercholesterolemia
Mitogen-Activated Protein Kinases
Machinery
Tumors
Cell Cycle
Cholesterol
Cells
Lipids
Plasmas
Growth
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells. / Borahay, Mostafa A.; Kilic, Gokhan; Yallampalli, Chrasekha; Snyder, Russell; Hankins, Gary; Al-Hendy, Ayman; Boehning, Darren.

In: Journal of Biological Chemistry, Vol. 289, No. 51, 19.12.2014, p. 35075-35086.

Research output: Contribution to journalArticle

Borahay, Mostafa A. ; Kilic, Gokhan ; Yallampalli, Chrasekha ; Snyder, Russell ; Hankins, Gary ; Al-Hendy, Ayman ; Boehning, Darren. / Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 51. pp. 35075-35086.
@article{4b52377b909b480a92dad806cf970824,
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 Gokhan Kilic and Chrasekha Yallampalli and Russell Snyder and Gary Hankins and Ayman Al-Hendy and Darren Boehning",
year = "2014",
month = "12",
day = "19",
doi = "10.1074/jbc.M114.583575",
language = "English (US)",
volume = "289",
pages = "35075--35086",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "51",

}

TY - JOUR

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

AU - Borahay, Mostafa A.

AU - Kilic, Gokhan

AU - Yallampalli, Chrasekha

AU - Snyder, Russell

AU - Hankins, Gary

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.

UR - http://www.scopus.com/inward/record.url?scp=84919360782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919360782&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.583575

DO - 10.1074/jbc.M114.583575

M3 - Article

VL - 289

SP - 35075

EP - 35086

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 51

ER -