Related Experiment Video
Updated: Mar 14, 2026
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Low carbohydrate diet prevents Mcl-1-mediated resistance to BH3-mimetics
Camila Rubio-Patiño1,2, Jozef P Bossowski1,2, Elodie Villa1,2
1Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Équipe "Contrôle Métabolique des Morts Cellulaires", Nice, France.
Abstract:
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.
Insights
Reducing dietary carbohydrates can decrease Mcl-1 expression in tumor cells, a key factor in cancer treatment resistance. This dietary change sensitizes lymphoma to chemotherapy, offering a potential safe therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Mcl-1 overexpression contributes to cancer treatment resistance.
- Targeting Mcl-1 expression is a critical goal in cancer therapy.
Purpose of the Study:
- To investigate the impact of dietary modulation on Mcl-1 expression in a Myc-driven lymphoma model.
- To identify specific dietary components that regulate Mcl-1 levels.
Main Methods:
- Utilized a Myc-driven lymphoma mouse model.
- Administered partial caloric restriction (25%) and isocaloric custom diets with varying carbohydrate content.
- Assessed Mcl-1 expression, AMPK activation, mTOR inhibition, and protein translation elongation.
Main Results:
- A 25% caloric reduction decreased Mcl-1 expression in tumor cells.
- Reduced carbohydrate intake (by 25%) significantly lowered Mcl-1 expression (by 50%) in lymphoma cells.
- Low carbohydrate diet activated AMPK, inhibited mTOR and eukaryotic elongation factor 2 (eEF2), blocking protein translation.
Conclusions:
- Dietary carbohydrate reduction is an effective strategy to decrease Mcl-1 expression in lymphoma.
- A low carbohydrate diet sensitizes Myc-driven lymphoma to ABT-737 therapy in vivo.
- Reducing carbohydrate intake may offer a safe approach to enhance anti-cancer therapeutics efficacy.
More Related Videos
10:44Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
