Evidence that the essential oil of bergamot modulates autophagy flux in human tumor cell lines

The long standing folk use of the essential oil (EO) of bergamot (Citrus bergamia Risso et Poiteau) as antiseptic is consistent with the observed antifungal and antimicrobial activities in conjunction with the most recently described increase of oxidative metabolism in human polimorphonuclear leukocytes [1]. We have previously reported that in SH-SY5Y human neuroblastoma cultures the EO of bergamot causes concentration-dependent cell death [2]. Here we now report compelling evidence demonstrating that in these cell cultures bergamot modulates autophagy in a concentration-dependent fashion, not linked to effects on cell survival and via mechanisms mTOR-independent. Enhanced LC3 conversion and degradation of the autophagic substrate p62 are still observed following suppression of Beclin-1 expression by siRNA. The observed effects are not cell line specific because enhanced LC3 lipidation and reduced p62 levels were also observed in bergamot exposed MCF7 human breast cancer cells. In depth investigation on the principle responsible for autophagy activation shows that limonene, the main terpene of the EO, is responsible for such an important effect of the phytocomplex. Autophagy is a complex and finely tuned cellular process that plays fundamental roles under physiological as well as pathological conditions; in fact, it has been implicated in severe human diseases, including cancer. Accordingly, our original observation is of great importance for putative clinical translation in chemotherapy.

References:

[1] Cosentino et al.,Phytother Res 2014; 28: 1232 – 1239

[2] Berliocchi et al. Food Chem Toxicol 2011; 49: 2780 – 2792