Research Papers:

Low carbohydrate diet prevents Mcl-1-mediated resistance to BH3-mimetics

Camila Rubio-Patiño, Jozef P. Bossowski, Elodie Villa, Laura Mondragón, Barbara Zunino, Emma Proïcs, Johanna Chiche, Frédéric Bost, Els Verhoeyen and Jean-Ehrland Ricci _

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Oncotarget. 2016; 7:73270-73279. https://doi.org/10.18632/oncotarget.12309

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Camila Rubio-Patiño1,2, Jozef P. Bossowski1,2, Elodie Villa1,2, Laura Mondragón1,2, Barbara Zunino1,2, Emma Proïcs1,2,3, Johanna Chiche1,2, Frédéric Bost2,4, Els Verhoeyen1,2, Jean-Ehrland Ricci1,2

1Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Équipe “Contrôle Métabolique des Morts Cellulaires”, Nice, France

2Université Nice Côte d’Azur, Inserm, C3M, France

3Centre Hospitalier Universitaire de Nice, Département d’Anesthésie Réanimation, Nice, France

4Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Équipe “Cellular and Molecular Physiopathology of Obesity and Diabetes”, Nice, France

Correspondence to:

Jean-Ehrland Ricci, email: [email protected]

Keywords: metabolism, cancer, resistance to treatment, Mcl-1, low carbohydrate diet

Received: May 27, 2016     Accepted: September 19, 2016     Published: September 28, 2016


Overexpression of Mcl-1 is implicated in resistance of several cancers to chemotherapeutic treatment, therefore identifying a safe way to decrease its expression in tumor cells represents a central goal. We investigated if a modulation of the diet could impact on Mcl-1 expression using a Myc-driven lymphoma model. We established that a partial reduction of caloric intake by 25% represents an efficient way to decrease Mcl-1 expression in tumor cells. Furthermore, using isocaloric custom diets, we observed that carbohydrates (CHO) are the main regulators of Mcl-1 expression within the food. Indeed, feeding lymphoma-bearing mice with a diet having 25% less carbohydrates was sufficient to decrease Mcl-1 expression by 50% in lymphoma cells. We showed that a low CHO diet resulted in AMPK activation and mTOR inhibition leading to eukaryotic elongation factor 2 (eEF2) inhibition, blocking protein translation elongation. Strikingly, a low CHO diet was sufficient to sensitize Myc-driven lymphoma-bearing mice to ABT-737-induced cell death in vivo. Thus reducing carbohydrate intake may represent a safe way to decrease Mcl-1 expression and to sensitize tumor cells to anti-cancer therapeutics.

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