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Downregulation of miR‐155 Contributes to The Anti‐proliferative Effects of The Soy Isoflavone Genistein in Estrogen Receptor Negative Breast Cancer
Author(s) -
De La Parra Columba,
CruzCollazo Ailed,
CastilloPichardo Linette,
Cubano Luis,
Redis Roxana,
Calin George,
Dharmawardhane Suranganie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.578.5
Subject(s) - genistein , estrogen receptor , cancer research , downregulation and upregulation , apoptosis , viability assay , cancer , breast cancer , medicine , biology , endocrinology , chemistry , biochemistry , gene
Consumption of the soy isoflavone genistein has been associated with reduced breast cancer risk. We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of estrogen receptor (ER) (‐) cancer cells in mice. The objective of this study was to investigate a role for the oncomir miR‐155 in the anticancer effects of genistein. At low physiologically relevant concentrations, genistein inhibited cell viability, induced apoptosis, and downregulated miR‐155 in the ER (‐) MDA‐MB‐435 and Hs578t breast cancer cells, without significantly affecting the viability or miR‐155 levels of ER (+) MCF‐7 breast cancer cells. In parallel, the pro‐apoptotic and anti‐cell proliferative miR‐155 targets FOXO3, PTEN, casein kinase, and p27 were upregulated in response to genistein in the ER (‐) cells. Ectopic expression of miR‐155 in the MDA‐MB‐435 and Hs578t cells decreased the effects of genistein on cell viability, and abrogated the effects of genistein on apoptosis and expression of pro‐apoptotic genes. We conclude that genistein‐mediated downregulation of miR‐155, a critical suppressor of apoptosis, contributes to the anticancer effects of genistein in ER (‐) breast cancer.