Multifaceted biological activities of linalool: antimicrobial, antibiofilm, cytotoxic, antiproliferative and caspase-3/7 activity.

Linalool is a natural bioactive monoterpene with antimicrobial, antibiofilm, and anticancer potential. Its multifaceted biological activity was investigated using microbial and mammalian cell-based models, addressing the limited integrated characterization of these effects. In this study, the antimicrobial and antibiofilm efficacy of linalool was evaluated against selected pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant S.aureus (MRSA), Klebsiella pneumoniae, and Candida albicans. Its cytotoxic, antiproliferative, and morphological effects were evaluated in the C6 glioma cell line at concentrations of 25, 50, 100, 200, 400, and 800µM, together with assessment of caspase-3/7 activity as an apoptosis-related marker. Linalool exhibited antimicrobial activity against all tested microorganisms and significantly suppressed biofilm formation. Among the tested strains, S. aureus was the most susceptible pathogen, showing the lowest minimum inhibitory concentration (MIC) (414.8µM) and the highest biofilm inhibition (64.77%). MTT analysis showed that linalool exerted dose-dependent cytotoxicity in C6-glioma cells after 24 h, with an IC50 of 563.3 µM (95%CI:370.3-871.7µM). Longitudinal trypan blue exclusion counting revealed that 400 µM linalool produced the strongest antiproliferative effect over 4 days, resulting in a 1.6-fold reduction in viable C6 cell numbers compared with the untreated control, accompanied by distinct morphological alterations. In addition, treatment with 400µM linalool increased executioner caspase-3/7 activity by up to 2.07-fold, which may be consistent with the involvement of apoptosis-related processes in linalool-induced cytotoxicity. These findings demonstrate the multifaceted biological activity of linalool, encompassing antimicrobial, antibiofilm, cytotoxic, and antiproliferative effects, with increased caspase-3/7 activity observed after linalool treatment, warranting further investigation of the underlying mechanisms.