Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms18122770
Keywords
omega-3; PUFA; chemoresistance; membrane; DHA; EPA
Funding
- Annual Institutional Award (Line 2-Action A)
- Universita degli studi di Milano, Italy
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Chemotherapy efficacy is strictly limited by the resistance of cancer cells. The omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic, but not still well elucidated, mechanisms. Nowadays, it is accepted that alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species, and lipid peroxidation are involved in omega-3 LCPUFA chemosensitizing effects. A crucial mechanism in the control of cell drug uptake and efflux is related to omega-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, omega-3 LCPUFAs often alter the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting a potential adjuvant role in the treatment of drug resistant cancers.
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