Aripiprazole undermines colorectal cancer cells' metabolic flexibility via MCT4
- The antipsychotic aripiprazole impaired mitochondrial function and OXPHOS-derived ATP in colorectal cancer cells; the compensatory glycolytic switch it triggered was not sustained.
- It suppressed the lactate transporter MCT4 by disrupting GNAQ–RXRα interaction and promoting nuclear RXRα, which represses MCT4; MCT4 overexpression blunted the growth inhibition.
- Together, mitochondrial dysfunction and blocked glycolytic compensation led to ATP depletion and apoptosis.
💡 Points Based on the abstract
Repurposing papers live or die on exposure, and this is the classic trap: antipsychotic concentrations in plasma are far below what cell-culture work usually needs, and aripiprazole is highly protein-bound. Until the effective in vitro concentration is set against achievable free levels, this is a mechanism for a tool-like dose. The MCT4 rescue experiment is the best part, though; it's a real functional test.
Aripiprazole collapses metabolic plasticity through the GNAQ/RXRα/MCT4 axis in colorectal cancer ↗