Metabolic Reprogramming by Ribitol Expands the Therapeutic Window of BETi JQ1 against Breast Cancer

Area of Science:

• Oncology
• Metabolomics
• Cancer Metabolism

Background:

• Cancer treatment faces challenges due to drug resistance.
• Metabolism's role in cancer is increasingly recognized for therapeutic potential.
• Ribitol was previously found to alter glycolysis in breast cancer cells.

Purpose of the Study:

• To investigate the combinatorial effects of ribitol with other anticancer drugs.
• To evaluate the synergistic potential of ribitol and JQ1 in breast cancer cells.
• To elucidate the molecular mechanisms underlying the observed synergy.

Main Methods:

• Tested combinations of ribitol with chrysin, lonidamine, GSK2837808A, CB-839, JQ1, and shikonin.
• Utilized breast cancer cell lines (MDA-MB-231, MCF-7, T-47D).
• Analyzed gene expression, cell proliferation, migration, and metabolic pathways.

Main Results:

• Ribitol and JQ1 synergistically inhibited proliferation and migration in MDA-MB-231 cells (triple-negative).
• Synergy involved downregulation of c-Myc, Bcl-2, Bcl-xL, Mcl-1, and upregulation of p53 and cytochrome C.
• Combined treatment differentially altered glycolysis, downregulating glucose-6-phosphate and lactate.

Conclusions:

• Combination therapy of ribitol and JQ1 demonstrates significant synergy in inhibiting breast cancer growth and inducing apoptosis.
• Targeting cancer metabolism, especially in combination, is crucial for effective treatment.
• Identifying specific cancer populations is key for successful clinical application of metabolomic interventions.