title: Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells.
abstract: 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.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. famicis@yahoo.com.|Health Center, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. famicis@yahoo.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. saveria.aquila@libero.it.|Health Center, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. saveria.aquila@libero.it.
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. catiamor@yahoo.com.
authors.forename: Catia
authors.initials: C
authors.lastname: Morelli
authors.affiliation: Health Center, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. guidosisters@yahoo.com.
authors.forename: Carmela
authors.initials: C
authors.lastname: Guido
authors.affiliation: Health Center, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. ms83.santoro@libero.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Department of Biology, Ecology and Earth Science (Di.B.E.S.T.), University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. perrotta@unical.it.
authors.forename: Ida
authors.initials: I
authors.lastname: Perrotta
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. doclollo@yahoo.com.
authors.forename: Loredana
authors.initials: L
authors.lastname: Mauro
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. docfrancy@yahoo.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giordano
authors.affiliation: Department of Biology, Ecology and Earth Science (Di.B.E.S.T.), University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. anigro@yahoo.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nigro
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. sebastiano.ando@unical.it.|Health Center, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. sebastiano.ando@unical.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Cosenza, Italy. mamissina@yahoo.it.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Panno
mesh_terms: D000078223:5-Methoxypsoralen; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D061986:MCF-7 Cells; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D000078223:5-Methoxypsoralen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D008730:Methoxsalen