Phloretin Induces Apoptosis in H-Ras MCF10A Human Breast Tumor Cells through the Activation of p53 via JNK and p38 Mitogen-Activated Protein Kinase Signaling

Mutations in Ras play a critical role in the development of human cancers, including breast cancer. We investigated the possible antiproliferative effects of the naturally occurring dihydrochalcone phloretin [2′,4′,6′‐trihydroxy‐3‐(4‐hydroxyphenyl)‐propiophenone] on H‐Ras‐transformed MCF10A human breast epithelial (H‐Ras MCF10A) cells. Phloretin suppressed H‐Ras MCF10A cell proliferation in a dose‐dependent manner and induced nuclear condensation in the cells, indicating that phloretin‐induced cell death occurs mainly via the induction of apoptosis. Prominent upregulation of p53 and Bax and cleavage of poly (ADP)‐ribose polymerase were also detected in the phloretin‐treated cells. Finally, phloretin markedly increased caspase‐3 activity as well as JNK and p38 mitogen‐activated protein kinase signaling. Our findings suggest that the phloretin‐induced apoptosis of breast tumor cells contributes to the chemopreventive potential of phloretin against breast cancer.