Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression
Annual summary rept. 1 Mar 2011-28 Feb 2012
PUERTO RICO UNIV SAN JUAN
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The effects of soy on cancer metastasis remain to be understood. A recent study by our laboratory reported that the soy isoflavone genistein reduced tumor growth and metastasis and downregulated cancer promoting genes in a nude mouse model with tumors established from MDA-MB-435 metastatic cancer cells. On the contrary individual daidzein and combined isoflavones genistein, daidzein, glycitein increased metastasis and upregulated the expression of genes that promote cell proliferation and survival, including eukaryotic protein synthesis initiation factors EIF4GI and EIF4E, critical members of the eIF4F protein synthesis initiation factor complex. The hypothesis of the proposed research is that soy isoflavones modulate breast cancer progression by specific regulation of eIF4F complex to affect the synthesis of cancer regulatory proteins. The purpose of this study is to investigate the molecular mechanisms by which soy isoflavones genistein and daidzein disparately regulate protein synthesis initiation in established breast cancer. Herein, we show that individual or combined soy isoflavones genistein, daidzein, and glycitein at physiological concentrations in MDA-MB-231 and SKBR3 did not change eIF4F complex or mTOR pathway. Treatment of MDA-MB- 435 cells with combined soy isoflavones increased eIF4E protein expression. Results with MDA-MB-231 and MDA-MB-435 metastatic cancer cell lines show that equol, but not daidzein, upregulated eIF4G without affecting eIF4E or its regulator 4E binding protein 4E-BP levels. Equol also increased c-Myc levels, as well as expression of IRES containing cell survival and proliferation promoting molecules. Daidzein metabolite equol may be a potent regulator of the cancer promoting effects of dietary daidzein.
- Medicine and Medical Research
- Food, Food Service and Nutrition