TitlePhloretin induces apoptosis in H-Ras MCF10A human breast tumor cells through the activation of p53 via JNK and p38 mitogen-activated protein kinase signaling.
Publication TypeJournal Article
Year of Publication2009
AuthorsKim, M-S, Kwon, JYeon, Kang, NJoo, Lee, KWon, Lee, HJoo
JournalAnn N Y Acad Sci
Volume1171
Pagination479-83
Date Published2009 Aug
ISSN1749-6632
KeywordsApoptosis, bcl-2-Associated X Protein, bcl-X Protein, Blotting, Western, Caspase 3, Cell Line, Transformed, Cell Proliferation, Dose-Response Relationship, Drug, Genes, ras, Humans, JNK Mitogen-Activated Protein Kinases, Mammary Glands, Human, MAP Kinase Signaling System, Molecular Structure, p38 Mitogen-Activated Protein Kinases, Phloretin, Poly(ADP-ribose) Polymerases, Tumor Suppressor Protein p53
Abstract

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.

DOI10.1111/j.1749-6632.2009.04692.x
Alternate JournalAnn. N. Y. Acad. Sci.
PubMed ID19723092