Journal Article

Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells

Santoro, Marta, Andò, Sebastiano, Perrotta, Ida, Nigro, Alessandra, Mauro, Loredana, Panno, Maria L., De Amicis, Francesca, Morelli, Catia, Aquila, Saveria, Giordano, Francesca, Guido, Carmela

2015

Overview

Background Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. Results In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy. Conclusions Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment.

• Publisher: BioMed Central,BioMed Central Ltd
• Subject: Analysis / Autophagy - drug effects / Autophagy - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - genetics / Cancer cells / Cancer Research / Care and treatment / Cell Line, Tumor / Cell Survival - drug effects / Cell Survival - genetics / Coumarins / Female / Gene Expression / Gene Expression Regulation, Neoplastic - drug effects / Genes, Reporter / Humans / MCF-7 Cells / Methoxsalen - analogs & derivatives / Methoxsalen - pharmacology / Oncology / Phenotype / Promoter Regions, Genetic / PTEN Phosphohydrolase - genetics / Up-Regulation / Vegetables