Publication

Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

Liu, S., Uppal, H., Demaria, M., Desprez, P-Y., Campisi, J. & Kapahi, P., 14-Dec-2015, In : Scientific Reports. 5, 11 p., 17895.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Liu, S., Uppal, H., Demaria, M., Desprez, P-Y., Campisi, J., & Kapahi, P. (2015). Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Scientific Reports, 5, [17895]. https://doi.org/10.1038/srep17895

Author

Liu, Su ; Uppal, Harpreet ; Demaria, Marco ; Desprez, Pierre-Yves ; Campisi, Judith ; Kapahi, Pankaj. / Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. In: Scientific Reports. 2015 ; Vol. 5.

Harvard

Liu, S, Uppal, H, Demaria, M, Desprez, P-Y, Campisi, J & Kapahi, P 2015, 'Simvastatin suppresses breast cancer cell proliferation induced by senescent cells' Scientific Reports, vol. 5, 17895. https://doi.org/10.1038/srep17895

Standard

Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. / Liu, Su; Uppal, Harpreet; Demaria, Marco; Desprez, Pierre-Yves; Campisi, Judith; Kapahi, Pankaj.

In: Scientific Reports, Vol. 5, 17895, 14.12.2015.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Liu S, Uppal H, Demaria M, Desprez P-Y, Campisi J, Kapahi P. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Scientific Reports. 2015 Dec 14;5. 17895. https://doi.org/10.1038/srep17895


BibTeX

@article{b275f6e0376940b988b7478dcce04589,
title = "Simvastatin suppresses breast cancer cell proliferation induced by senescent cells",
abstract = "Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance.",
author = "Su Liu and Harpreet Uppal and Marco Demaria and Pierre-Yves Desprez and Judith Campisi and Pankaj Kapahi",
year = "2015",
month = "12",
day = "14",
doi = "10.1038/srep17895",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

AU - Liu, Su

AU - Uppal, Harpreet

AU - Demaria, Marco

AU - Desprez, Pierre-Yves

AU - Campisi, Judith

AU - Kapahi, Pankaj

PY - 2015/12/14

Y1 - 2015/12/14

N2 - Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance.

AB - Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance.

U2 - 10.1038/srep17895

DO - 10.1038/srep17895

M3 - Article

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 17895

ER -

ID: 26937099