Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.

ABSTRACT:

Purpose

Dual-Interventions targeting glucose and oxidative metabolism are receiving increasing attention in cancer therapy. Sorafenib (S) and Metformin (M), two gold-standards in liver cancer, are known for their mitochondrial inhibitory capacity. Fasting, a glucose-limiting strategy, is also emerging as chemotherapy adjuvant. Herein, we explore the anti-carcinogenic response of nutrient restriction in combination with sorafenib:metformin (NR-S:M).

Results

Our data demonstrates that, independently of liver cancer aggressiveness, fasting synergistically boosts the anti-proliferative effects of S:M co-treatment. Metabolic and Cellular plasticity was determined by the examination of mitochondrial and glycolytic activity, cell cycle modulation, activation of cellular apoptosis,

SUBMITTER: Lopez-Canovas JL 

PROVIDER: S-EPMC11850423 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature