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Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice
Simona Delle Monache1, Patrizia Sanità, Elena Trapasso
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
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.
Insights
Bergamot juice (BJ) shows anti-tumor potential by inhibiting cancer cell growth and migration. It halts the cell cycle and alters cell adhesion without causing cell death, suggesting novel therapeutic avenues.
Area of Science:
- Oncology
- Natural Product Chemistry
- Cell Biology
Background:
- Flavonoid-rich natural products exhibit significant biological activity.
- Bergamot (Citrus Bergamia) juice (BJ) is rich in bioactive compounds.
- Understanding the molecular mechanisms of natural products against cancer is crucial.
Purpose of the Study:
- To investigate the in vitro anti-tumoral activity of bergamot juice (BJ).
- To determine the molecular interactions of BJ with cancer cells.
- To explore BJ's potential in cancer treatment strategies.
Main Methods:
- Exposure of various cancer cell lines to BJ.
- Analysis of cell growth rate, cell cycle, apoptosis, and cellular morphology.
- Assessment of cell adhesion, actin filament integrity, and focal adhesion kinase (FAK) activity.
- Investigation of neural cell adhesion molecule (NCAM) and FAK interactions.
Main Results:
- BJ significantly reduced the growth rate of cancer cell lines, notably neuroblastoma (SH-SY5Y) cells.
- BJ induced G1 phase cell cycle arrest and morphological changes, increasing detached cells.
- BJ inhibited cell adhesion and migration by impairing actin filaments and reducing active focal adhesion kinase (FAK).
- BJ appeared to disrupt the association between neural cell adhesion molecule (NCAM) and FAK.
Conclusions:
- Bergamot juice exhibits anti-proliferative effects on cancer cells without inducing cytotoxicity or apoptosis.
- BJ inhibits key molecular pathways associated with cancer cell migration and adhesion.
- BJ's impact on cell cycle, adhesion, and migration pathways suggests potential as a novel anti-cancer therapeutic agent.
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