Abstract
Based on the growing deal of data concerning the biological activity of flavonoid-rich natural products, the aim of the present study was to explore in vitro the potential anti-tumoral activity of Citrus Bergamia (bergamot) juice (BJ), determining its molecular interaction with cancer cells. Here we show that BJ reduced growth rate of different cancer cell lines, with the maximal growth inhibition observed in neuroblastoma cells (SH-SY5Y) after 72 hs of exposure to 5% BJ. The SH-SY5Y antiproliferative effect elicited by BJ was not due to a cytotoxic action and it did not induce apoptosis. Instead, BJ stimulated the arrest in the G1 phase of cell cycle and determined a modification in cellular morphology, causing a marked increase of detached cells. The inhibition of adhesive capacity on different physiologic substrates and on endothelial cells monolayer were correlated with an impairment of actin filaments, a reduction in the expression of the active form of focal adhesion kinase (FAK) that in turn caused inhibition of cell migration. In parallel, BJ seemed to hinder the association between the neural cell adhesion molecule (NCAM) and FAK. Our data suggest a mechanisms through which BJ can inhibit important molecular pathways related to cancer-associated aggressive phenotype and offer new suggestions for further studies on the role of BJ in cancer treatment.
Highlights
Citrus Bergamia Risso & Poiteau, a small tree belonging to the Rutaceae family, is cultivated almost exclusively along the southern coast of Calabria region (Italy), where the particular environmental conditions are favourable for its cultivation
Bergamot juice (BJ) was able to inhibit the proliferation of several cancer cell lines with the maximal achievement in the SH-SY5Y neuroblastoma cells, in which caused arrest of the cell cycle accompanied with a marked reduction of cell adhesion mediated by an impairment of the actin network
The growth inhibitory effect of BJ is not mediated by a cytotoxic effect, because at the concentrations tested in this study we did not observe significant increase in cell death
Summary
Citrus Bergamia Risso & Poiteau, a small tree belonging to the Rutaceae family, is cultivated almost exclusively along the southern coast of Calabria region (Italy), where the particular environmental conditions are favourable for its cultivation. Naringin, one of the flavonoids present in the BJ, was able to reduce the high glucose-induced ICAM-1 expression via the p38 MAPK signalling pathway, contributing to the inhibition of monocyte adhesion to endothelial cells [19]. It has been demonstrated that flavanone and 29-OH flavanone perturb the invasion and metastasis of lung cancer cells probably through inactivation of ERK 1/2 and p38MAPK signalling pathways [20]. Much of these effects can be attributable to the ability of flavonoids to interact with mitogenic or migratory signalling pathways but the precise underlying molecular mechanisms remain largely unclear
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