Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein

• Published in: Nutrition and cancer 2016-01, Vol.68 (1), p.154-164
• Main Authors: de la Parra, Columba, Castillo-Pichardo, Linette, Cruz-Collazo, Ailed, Cubano, Luis, Redis, Roxana, Calin, George A, Dharmawardhane, Suranganie
• Format: Article
• Language: English
• Subjects: antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Survival - drug effects; cell viability; Down-Regulation; Female; genes; genistein; Genistein - pharmacology; Humans; mammary neoplasms (animal); MCF-7 Cells; Metastasis; mice; microRNA; MicroRNAs - analysis; neoplasm cells; non-specific serine/threonine protein kinase; PTEN Phosphohydrolase - analysis; Soy products
• ISSN: 1532-7914; 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2016.1115104

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.