A Quantum-Biochemical Model of AA-5-HT-Induced Cytotoxicity in HL-60 Cells via FAAH Inhibition and Cannabinoid Receptor–Mediated Signal Interference

Acute promyelocytic leukemia (APL) remains one of the most aggressive hematological malignancies, necessitating the discovery of novel therapeutic agents with improved efficacy and reduced toxicity. N-arachidonoyl-5-hydroxytryptamine (AA-5-HT), a hybrid indole–fatty acid amide compound isolated from Dialium corbisieri , has demonstrated potent cytotoxic activity in HL-60 leukemia cells, characterized by G 1 phase cell cycle arrest at low micromolar concentrations (2.3µM). Despite these promising findings, its mechanism of action remains incompletely understood. Here, we propose a quantum-biochemical hypothesis integrating molecular pharmacology with principles derived from quantum theory to explain AA-5-HT-induced cytotoxicity. We hypothesize that AA-5-HT inhibits fatty acid amide hydrolase (FAAH), leading to accumulation of anandamide (AEA), which in turn activates Gi/o-coupled cannabinoid receptors (CB 1 /CB 2 ). This activation suppresses the PI3K/AKT signaling pathway, resulting in decreased AKT phosphorylation, upregulation of cyclin-dependent kinase inhibitors (p21, p27), reduced retinoblastoma protein phosphorylation, and consequent G 1 arrest. From a quantum-biochemical perspective, AA-5-HT acts as a perturbator that shifts intracellular signaling probabilities, promoting destructive interference of pro-survival pathways and stabilizing a non-proliferative cellular state. This framework provides a novel conceptual model for understanding anticancer mechanisms and suggests new experimental directions for validating AA-5-HT as a therapeutic candidate.