The phytochemical profiles (total phenolics, anthocyanins, ferulic acid, carotenoids) and antioxidant activities of five types corn (white, yellow, high carotenoid, blue, red) processed into masa, tortillas, tortilla chips were studied. nixtamalization process significantly (p < 0.05) reduced total phenolics when compared to raw grains. Nixtamalized grains exhibited higher concentration free soluble conjugated acid had lower concentrations bound than unprocessed Among products, there was...

Translation initiation of most mammalian mRNAs is mediated by a 5' cap structure that binds eukaryotic factor 4E (eIF4E). However, inactivation eIF4E does not impair translation many capped mRNAs, suggesting an unknown alternate mechanism may exist for cap-dependent but eIF4E-independent translation. We show DAP5, eIF4GI homolog lacks binding, utilizes eIF3d to facilitate approximately 20% mRNAs. Genome-wide transcriptomic and translatomic analyses indicate DAP5 required transcription...

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 role novel oncogenic microRNA (miRNA) miR-155 anticancer effects breast cancer. effect determined on cell viability, apoptosis, expression its targets. At low physiologically relevant concentrations, viability induces apoptosis Hs578t cells, without affecting nonmetastatic MCF-7 cells. In...

Cancer cell plasticity enables survival in harsh physiological environments and fate transitions such as the epithelial-to-mesenchymal transition (EMT) that underlies invasion metastasis. Using genome-wide transcriptomic translatomic studies, an alternate mechanism of cap-dependent mRNA translation by DAP5/eIF3d complex is shown to be essential for metastasis, EMT, tumor directed angiogenesis. carries out selective mRNAs encoding EMT transcription factors regulators, migration integrins,...

Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies inhibit metastatic cancer. The Rho family GTPase Rac an ideal target for anti-metastatic therapy, because key molecular switch that activated by myriad cell surface receptors promote migration/invasion survival. Previously, we reported design development EHop-016, small molecule compound, which inhibits activity cells with...

Abstract Regulatory T cells (Treg cells) inhibit effector and maintain immune system homeostasis. Treg cell maturation in peripheral sites requires inhibition of protein kinase mTORC1 TGF-beta-1 (TGF-beta). While synthesis, downregulates it, leaving unanswered how achieve essential mRNA translation for development suppression activity. Using human CD4 + differentiated culture genome-wide transcription profiling, here we report that TGF-beta transcriptionally reprograms naive to express...

Breast cancer treatment has advanced significantly, particularly for estrogen receptor-positive (ER+) tumors. Tamoxifen, an antagonist, is widely used; however, approximately 40% of patients develop resistance. Recent studies indicate that microRNAs, especially miR-155, play a critical role in this Our analysis MCF-7 tamoxifen-sensitive (TAM-S) and tamoxifen-resistant (TAM-R) cells revealed miR-155 significantly upregulated TAM-R cells. Overexpression TAM-S increased resistance to tamoxifen....

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. We previously demonstrated that IL-24 leads to apoptosis cancer cells through kinase A (PKA) activation human breast cells. To better understand the mechanism by which induces apoptosis, we analyzed role of glycogen synthase kinase-3 beta (GSK3β), highly conserved serine/threonine and downstream target PKA. Our studies show for first time GSK3β inhibited following treatment prostate showed inhibition mediated...

Dietary soy is thought to be cancer-preventive; however, the beneficial effects of on established breast cancer controversial. We recently demonstrated that dietary daidzein or combined isoflavones (genistein, daidzein, and glycitein) increased primary mammary tumor growth metastasis. Cancer-promoting molecules, including eukaryotic protein synthesis initiation factors (eIF) eIF4G eIF4E, were up-regulated in tumors from mice received daidzein. Herein, we show eIF expression extracts after...

Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, may also have a role in promoting cancer, which has yet be clarified. We previously reported that equol, metabolite of the isoflavone daidzein, advance potential via up-regulation eukaryotic initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER-) metastatic cells, equol induced elevated levels eIF4G, were associated with increased...

Abstract Triple negative breast cancer (TNBC) is one of the most aggressive subtypes cancer, accounting for 10-15% all cancers in women. The frequency metastasis TNBC disproportionally high compared to other and primary cause patient mortality. At cellular level, TNBC's nature demands rapid adaptation tumor cells navigate stressors survival metastatic transformation. These adaptations include a cell’s ability reprogram its metabolism regulate mRNA translation control, coordinating...

Consumption of the soy isoflavone genistein has been associated with reduced breast cancer risk. We previously reported that dietary inhibits mammary tumor growth and metastasis estrogen receptor (ER) (‐) cells in mice. The objective this study was to investigate a role for oncomir miR‐155 anticancer effects genistein. At low physiologically relevant concentrations, inhibited cell viability, induced apoptosis, downregulated ER MDA‐MB‐435 Hs578t cells, without significantly affecting...

Abstract The Rho GTPase Rac is a central regulator of cancer cell migration/invasion that has been implicated with metastasis. Therefore, we designed and developed small molecule compounds specifically target in metastatic cells. We recently reported the characterization EHop-016 as inhibitor cells, where was shown to inhibit activity an IC50 1 μM. At higher concentrations (&amp;gt;10 μM) reduced viability inhibited related Cdc42, but not Rho. decreased activation by oncogenic guanine...

Abstract Regulatory T cells (Tregs) maintain immune system homeostasis in the organism. In tumor microenvironment, however, Tregs can hinder antitumor response. Treg maturation peripheral sites (pTregs) requires inhibition of protein kinase mTORC1, which paradoxically blocks mRNA translation. mTORC1 phosphorylates (inactivates) 4E-BP1, a negative regulator translation initiation factor eIF4E. When is active, 4E-BP1 hyperphosphorylated and releases eIF4E, then bind cap structure promote eIF4F...

Abstract Translational control and metabolic reprogramming are hallmarks of advanced cancers. Important genes involved in cancer progression express mRNAs that selectively translated, including regulators cell metabolism. Cancer cells acquire an altered metabolism, switching from oxidative phosphorylation (OXPHOS) to a glycolytic phenotype (Warburg effect), increase reliance on alternate pathways support growth, proliferation, metastasis. Triple-negative breast (TNBC), one the most...

Abstract We previously reported that dietary genistein significantly inhibits mammary tumor growth and metastasis of estrogen receptor (ER) (-) MDA-MB-435 metastatic cancer cells in immunocompromised mice. The purpose the present study is to investigate molecular mechanisms ER breast cells. report at low physiologically relevant concentrations, cell induces apoptosis Hs578t To mechanism by which regulates viability, a panel microRNAs (miRNAs) were tested for differential expression response...

The effects of soy isoflavones on established breast cancer remain to be understood. We recently reported that dietary daidzein increased primary mammary tumor growth and metastasis, upregulated eukaryotic protein synthesis initiation factors (eIF) eIF4G eIF4E. eIF expression in extracts mice after diets was associated with mRNAs internal ribosome entry sites (IRES). Results metastatic cell lines show the vivo can recapitulated by its metabolite equol. Equol viability up‐regulated gene...

Abstract The role of dietary soy in cancer has been the subject intense investigation and is thought to be preventive. However, beneficial effects on established breast controversial. We recently demonstrated that daidzein combined isoflavones (genistein, daidzein, glycitein) promoted progression a nude mouse model by increasing both primary mammary tumor growth metastasis. Dietary significantly upregulated promoting molecules including eukaryotic protein synthesis initiation factors (eIF)...

Abstract Metastasis is the cause of 90% cancer-related deaths. Selective mRNA translation has been found to be crucial for breast cancer development, progression and metastasis; however, there a poor biological mechanistic understanding role in these processes. Our work others have pioneered an translational regulation cancer. We previously shown that overexpression initiation factor eIF4GI advanced cells selectively increases mRNAs encoding survival, cell cycle inhibition, DNA damage repair...

Equol, one of the most studied metabolites soy isoflavone daidzein, is associated with both anticancer and pro‐cancer effects in breast cancer. These contradictory results have been shown to be concentration dependent, where high equol concentrations reduced non‐metastatic cancer cell growth proliferation, risk. However, we that at low physiological dietary concentrations, increases tumor metastasis metastatic models. Also, expression eukaryotic initiation factor 4G (eIF4G), increasing...