Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells

Giovanna Talarico, Stefania Orecchioni, Katiuscia Dallaglio, Francesca Reggiani, Patrizia Mancuso, Angelica Calleri, Giuliana Gregato, Valentina Labanca, Teresa Rossi, Douglas M Noonan, Francesco Bertolini, Adriana Albini

Research output: Contribution to journalArticle

Abstract

Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells.

Original languageEnglish
Article number18673
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jan 5 2016

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Cellular Microenvironment
Atenolol
Metformin
Aspirin
Breast Neoplasms
Triple Negative Breast Neoplasms
Apoptosis
White Adipose Tissue
Pericytes
AMP-Activated Protein Kinases
Tumor Microenvironment
Cellular Structures
Growth
Electron Transport
Endothelial Cells

ASJC Scopus subject areas

  • General

Cite this

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title = "Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells",
abstract = "Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells.",
author = "Giovanna Talarico and Stefania Orecchioni and Katiuscia Dallaglio and Francesca Reggiani and Patrizia Mancuso and Angelica Calleri and Giuliana Gregato and Valentina Labanca and Teresa Rossi and Noonan, {Douglas M} and Francesco Bertolini and Adriana Albini",
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T1 - Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells

AU - Talarico, Giovanna

AU - Orecchioni, Stefania

AU - Dallaglio, Katiuscia

AU - Reggiani, Francesca

AU - Mancuso, Patrizia

AU - Calleri, Angelica

AU - Gregato, Giuliana

AU - Labanca, Valentina

AU - Rossi, Teresa

AU - Noonan, Douglas M

AU - Bertolini, Francesco

AU - Albini, Adriana

PY - 2016/1/5

Y1 - 2016/1/5

N2 - Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells.

AB - Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells.

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