Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar.
OBJECTIVE
The aim of this study was to evaluate the antiproliferative activity in breast cancer cells and the inhibition of tumorigenesis in pre-neoplastic cells of a new apple cultivar with reddish pulp, called the Pelingo apple.


METHODS
The antiproliferative activity was evaluated in MCF-7 and MDA-MB-231 human breast cancer cells. The inhibition of tumorigenesis was performed in JB6 promotion-sensitive (P+) cells.


RESULTS
Results showed that Pelingo apple juice is characterized by a very high polyphenol content and strongly inhibited breast cancer cell proliferation. Its antiproliferative activity was found to be higher than the other five apple juices tested. Pelingo juice induced cell accumulation in the G2/M phase of the cell cycle and autophagy through overexpression of p21, inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) activity and an increase in lipidated microtubule-associated protein-1 light chain-3 beta (LC3B). Remarkably, Pelingo juice inhibited the 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)-induced tumorigenesis of JB6 P+ cells, suppressing colony formation in semi-solid medium and TPA-induced ERK1/2 phosphorylation.


CONCLUSIONS
Our data indicate that the Pelingo apple is rich in food components that can markedly inhibit in vitro tumorigenesis and growth of human breast cancer cells and could provide natural bioactive non-nutrient compounds, with potential chemopreventive activity.
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Giuditta Fiorella
GF
Schiavano
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Mauro
M
De Santi
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Giorgio
G
Brandi
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Mirco
M
Fanelli
Department of Earth, Life and Environmental Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Anahi
A
Bucchini
Department of Earth, Life and Environmental Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Laura
L
Giamperi
Department of Earth, Life and Environmental Sciences, University of Urbino "Carlo Bo", Urbino (PU), Italy.
Giovanna
G
Giomaro
D000872:Anthocyanins / Q000032:analysis; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000067030:Fruit and Vegetable Juices / Q000032:analysis*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D027845:Malus / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D059808:Polyphenols / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects
D000872:Anthocyanins; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008869:Microtubule-Associated Proteins; D059808:Polyphenols; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate