Bisabolol as a natural anticancer agent: molecular insights and therapeutic potential in oncology.

Abstract

α-Bisabolol is a naturally derived monocyclic sesquiterpene, abundantly present in German chamomile (Matricaria recutita) and various other aromatic plants and is also increasingly accessible via metabolic engineering platforms. The physicochemical profile and ADMET characteristics of α-bisabolol, suggest a high gastrointestinal absorption, and minimal P-glycoprotein and CYP450 interactions, which validate its drug-like potential. The multi-protein target engagement and predicted activity spectrum of α-bisabolol have been discussed in the manuscript by using in silico tools (SwissTargetPrediction and PASS), which aligns with the experimental anticancer results of α-bisabolol in leukemia, pancreatic, lung, and glioblastoma models. Mechanistically, the anticancer profile of α-bisabolol arises from the induction of mitochondrial apoptosis, disruption of PI3K/Akt/FAK/BRAF pathways, modulation of lipid-raft-associated Bid protein, and dysregulation of autophagy. The design and bioactivity of novel chemical derivatives (e.g., acyl, glycoside, and thiosemicarbazone analogs) and delivery systems (cyclodextrin inclusion complexes, PLGA nanoparticles), emphasizing improvements in solubility, potency, and systemic delivery have also been comprehensively discussed in this review. Finally, a critical evaluation of the clinical translation barriers including poor aqueous solubility, limited in vivo pharmacokinetics, CYP2C9/CYP2J-mediated metabolism, and formulation challenges of α-bisabolol have been succinctly provided. Overall, this review integrates phytochemistry, polypharmacology, mechanistic validation, and translational hurdles, thereby offering a novel roadmap for developing α-bisabolol as a viable anticancer therapeutic.