The naringenin-induced proapoptotic effect in breast cancer cell lines holds out against a high bisphenol a background.
Fruit and vegetable consumption has generally been associated with the prevention or suppression of cancer. However, food could contain a multitude of chemicals (e.g., bisphenol A; BPA) that could synergize or antagonize the effects of diet-derived compounds. Remarkably, food containers (e.g., water and infant bottles) are the largest source of exposure to BPA for human beings. Here, the effects of the coexposure of naringenin (Nar, 1.0 × 10(-9) M to 1.0 × 10(-4) M) and BPA (1.0 × 10(-5) M) in estrogen-dependent breast cancer cell lines expressing (i.e., MCF-7 and T47D) or not expressing (i.e., MDA-MB-231) estrogen receptor α (ERα) are reported. Although both Nar and BPA bind to ERα, they induce opposite effects on breast cancer cell growth. BPA induces cell proliferation, whereas Nar only decreases the number of ERα-positive cells (i.e., MCF-7 and T47D). Notably, even in the presence of BPA, Nar impairs breast cancer cell proliferation by activating caspase-3. The molecular pathways involved require p38 activation, whereas, the BPA-induced AKT activation is completely prevented by the Nar treatment. As a whole, Nar maintains its proapoptotic effects even in the presence of the food contaminant BPA, thus, enlarging the chemopreventive potential of this flavanone.
Department of Biology, University Roma Tre, Viale G. Marconi 446, I-00146 Roma, Italy.
Pamela
P
Bulzomi
Alessandro
A
Bolli
Paola
P
Galluzzo
Filippo
F
Acconcia
Paolo
P
Ascenzi
Maria
M
Marino
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005506:Food Contamination; D006801:Humans; D010636:Phenols / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D053148:Caspase 3; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D044950:Flavanones; D010636:Phenols; D048051:p38 Mitogen-Activated Protein Kinases; C005273:naringenin; C006780:bisphenol A; D000098826:Bisphenol A Compounds