Lemon Grass Essential Oil does not Modulate Cancer Cells Multidrug Resistance by Citral—Its Dominant and Strongly Antimicrobial Compound

Importance of the Topic

Lemongrass essential oil and its dominant compound citral are renowned for their broad-spectrum antimicrobial, antibiofilm, and biological activities. Their capacity to counteract multidrug resistance in pathogenic bacteria and cancer cells addresses a critical challenge in contemporary medicine and food safety.

Objectives and Overview of the Study

This study aimed to compare the crude lemongrass essential oil and pure citral with respect to:

• Chemical profiling by GC–HRMS.
• Antimicrobial efficacy against Gram-positive, Gram-negative, yeast, and resistant strains.
• Anti-biofilm and quorum sensing inhibition activities.
• Modulation of multidrug resistance in MRSA and doxorubicin-resistant ovarian carcinoma cells.

Methodology and Instrumentation

• Vacuum steam distillation for essential oil extraction from fresh Cymbopogon citratus leaves.
• GC–HRMS (Agilent 7200b Q-TOF, HP-5MS column) for volatile compound analysis.
• Broth microdilution and resazurin assays to determine IC50 and MIC values.
• Static 96-well biofilm assays to evaluate adhesion inhibition and mature biofilm disruption.
• Vibrio campbellii bioreporter strains measuring AI-1 and AI-2 quorum sensing via luminescence.
• Pgp-Glo ATPase assay to assess P-glycoprotein efflux pump inhibition.
• Resazurin viability assay on A2780 and A2780/ADR ovarian carcinoma lines co-treated with doxorubicin.

Main Results and Discussion

• Oil yield was 0.5% (w/w) with 63% citral content (neral and geranial).
• Citral was 10–100× more potent than the crude oil against bacteria and fungi (IC50 2–109 µL/L vs. 177–2626 µL/L).
• Citral and oil both inhibited P. aeruginosa and S. aureus biofilm adhesion, but only citral disrupted mature biofilms effectively (IC50 0.1 mL/L vs. 7.3 mL/L for oil).
• Both samples reduced AI-1 and AI-2 quorum sensing; citral exhibited stronger inhibition at lower concentrations.
• Lemongrass oil, but not citral, sensitized MRSA (9.6-fold) and doxorubicin-resistant ovarian carcinoma cells (1.8-fold), suggesting efflux pump targeting.
• Oil inhibited human P-glycoprotein ATPase activity, whereas citral showed no inhibition, indicating the oil’s role in modulating drug efflux.

Benefits and Practical Applications

• Citral’s strong antimicrobial and anti-quorum sensing activities support its use in preservation and disinfection.
• The complete essential oil offers synergistic components that enhance antibiotic and chemotherapy efficacy via efflux pump inhibition.
• Direct application of the oil can serve as a natural adjuvant to overcome multidrug resistance in medical and industrial settings.

Future Trends and Potential Applications

• Isolation and characterization of additional oil components with resistance-modulating effects.
• Development of combined formulations pairing essential oil with standard antibiotics or chemotherapeutics.
• Exploration of the oil’s activity against other efflux pump families and resistant pathogens.
• Design of anti-biofilm coatings and materials for healthcare and food-contact surfaces.

Conclusion

While citral is chiefly responsible for lemongrass oil’s antimicrobial and anti-biofilm activities, the full essential oil uniquely modulates multidrug resistance in bacteria and cancer cells through efflux pump inhibition. Its direct use as a natural mixture may offer a pragmatic strategy to enhance existing therapeutic protocols.

References

• Viktorová J, Stupák M, Řehořová K, et al. Lemon Grass Essential Oil does not Modulate Cancer Cells Multidrug Resistance by Citral—Its Dominant and Strongly Antimicrobial Compound. Foods. 2020;9(5):585.