8-Prenylnaringenin inhibits epidermal growth factor-induced MCF-7 breast cancer cell proliferation by targeting phosphatidylinositol-3-OH kinase activity.
8-Prenylnaringenin (8PN), one of the strongest plant-derived oestrogen receptors (ERs) ligand, has been suggested to have potential cancer chemo-preventive activities and anti-angiogenic properties. Because published data suggest that ERs serve as nodal point that allows interactions between hormones and growth factors mediated pathways, we decided to investigate the effects exerted by 8PN on Epidermal growth factor (EGF)-elicited pathways in breast cancer cells. Here we show that in ER positive MCF-7 cells, 8PN interferes with EGF induced cell proliferation by strongly inhibiting activation of PI(3)K/Akt pathway, without affecting EGFR expression or tyrosine phosphorylation, and exerting a synergistic activation of Erk1/2 phosphorylation. Moreover, we demonstrate that 8PN is a direct inhibitor of PI(3)K activity as it is shown by in vitro experiments with the purified enzyme and by its inability to impair serine phosphorylation of a constitutive active form of Akt. These findings suggest that inhibition of PI(3)K is a novel mechanism which contributes to 8PN activity to inhibit cancer cell survival and EGF induced proliferation.
Brunelli
Elisa
E
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Via Bovio 6, Novara, Italy.
Pinton
Giulia
G
Chianale
Federica
F
Graziani
Andrea
A
Appendino
Giovanni
G
Moro
Laura
L
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D048789:Phytoestrogens / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C119737:8-prenylnaringenin; D044950:Flavanones; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases