TY - JOUR
T1 - Soy isoflavone genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein
AU - De La Parra, Columba
AU - Castillo-Pichardo, Linette
AU - Cruz-Collazo, Ailed
AU - Cubano, Luis
AU - Redis, Roxana
AU - Calin, George A.
AU - Dharmawardhane, Suranganie
N1 - Funding Information:
This work was sponsored by the United States Army/Breast Cancer Research Program W81XWH-11-1-0199 to CDP; National Institutes of Health (NIH)/National Institute of General Medical Sciences SC3GM084824 to SD; NIH/National Institute on Minority Health and Health Disparities (NIMHD) G12RR035051 to the University of Puerto Rico Medical Sciences Campus; and NIH/NIMHD G12RR003035, NIH/ NIMHHD Research Centers in Minority Institutions (RCMI) 8G12MD007583.
Publisher Copyright:
© 2016 Taylor & Francis Group, LLC.
PY - 2016/1/2
Y1 - 2016/1/2
N2 - We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer.
AB - We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer.
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U2 - 10.1080/01635581.2016.1115104
DO - 10.1080/01635581.2016.1115104
M3 - Article
C2 - 26771440
AN - SCOPUS:84957962537
SN - 0163-5581
VL - 68
SP - 154
EP - 164
JO - Nutrition and cancer
JF - Nutrition and cancer
IS - 1
ER -