Enhanced Cholesterol-Lowering and Antioxidant Activities of Soymilk by Fermentation with Lactiplantibacillus plantarum KML06.

This study aimed to evaluate the cholesterol-lowering and antioxidant activities of soymilk fermented with probiotic Lactobacillaceae strains and to investigate the production of related bioactive compounds. Lactiplantibacillus plantarum KML06 (KML06) was selected for the fermentation of soymilk because it has the highest antioxidant, cholesterol-lowering, and ß-glucosidase activities among the 10 Lactobacillaceae strains isolated from kimchi. The genomic information of strain KML06 was analyzed. Moreover, soymilk fermented with KML06 was evaluated for growth kinetics, metabolism, and functional characteristics during the fermentation period. The number of viable cells, which was similar to the results of radical scavenging activities and cholesterol assimilation, as well as the amount of soy isoflavone aglycones, daidzein, and genistein, was the highest at 12 h of fermentation. These results indicate that soymilk fermented with KML06 can prevent oxidative stress and cholesterol-related problems through the production of soy isoflavone aglycones.

Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to PPAR ligands.

BACKGROUND: The peroxisome proliferator activated receptor (PPAR) subgroup of the nuclear hormone receptor superfamily is activated by a variety of natural and synthetic ligands. PPARs can heterodimerize with retinoid X receptors, which have homology to other members of the nuclear receptor superfamily. Ligand binding to PPAR/RXRs results in recruitment of transcriptional coactivator proteins such as steroid receptor coactivator 1 (SRC-1) and CREB binding protein (CBP). Both SRC-1 and CBP are histone acetyltransferases, which by modifying nucleosomal histones, produce more open chromatin structure and increase transcriptional activity. Nuclear hormone receptors can recruit limiting amounts of coactivators from other transcription factor binding sites such as AP-1, thereby inhibiting the activity of AP-1 target genes. PPAR and RXR ligands have been used in experimental breast cancer therapy. The role of coactivator expression in mammary tumorigenesis and response to drug therapy has been the subject of recent studies. METHODS: We examined the effects of loss of SRC-1 on MMTV-neu mediated mammary tumorigenesis. RESULTS: SRC-1 null mutation in mammary tumor prone mice increased the tumor latency period, reduced tumor proliferation index and metastasis, inhibited response to PPAR and RXR ligands, and induced genes involved in mammary gland differentiation. We also examined human breast cancer cell lines overexpressing SRC-1 or CBP. Coactivator overexpression increased cellular proliferation with resistance to PPAR and RXR ligands and remodeled chromatin of the proximal epidermal growth factor receptor promoter. CONCLUSIONS: These results indicate that histone acetyltransferases play key roles in mammary tumorigenesis and response to anti-proliferative therapies.

Tumor initiating cancer stem cells from human breast cancer cell lines.

Breast cancer is composed of heterogeneous cell populations with different biological properties. The capacity to form tumors resides in a small group of cells termed tumor initiating cells or cancer stem cells. Tumor initiating cells have been identified in a variety of cancers by sorting of subpopulations based on cell surface markers and transplantation into animal models. Tumor initiating cells have the important feature of self renewal, which is a property in common with stem cells. We examined established breast cancer lines for cells with tumor initiating properties. A dye efflux side population in MCF7 and T47D lines expressed markers of breast cancer stem cells. The side population represents a distinct morphologic and functional subpopulation within the human breast cancer cell lines MCF7 and T47D. The side population from human breast cancer cell lines was able to initiate tumors in vivo. The side population cells from human breast cancer cell lines were more resistant to ionizing radiation than the non-side population. We concluded that tumor initiating cells exist in established human breast cancer cell lines.

Jun amino-terminal kinase 1 activation promotes cell survival in ErbB2-positive breast cancer.

BACKGROUND: Downstream signaling is a key component of Her2/neu overexpression in human breast cancer. Major survival pathways downstream of Her2/neu include mitogen and stress activated protein kinases (ERK, JNK, p38). MATERIALS AND METHODS: MAPK protein expression was examined in mouse and human cancer tissue. MAPK expression was inhibited by genetic and pharmacologic methods in human breast cancer cell lines. The effects of MAPK inhibition on tumor formation in a preclinical model were determined. RESULTS: It was shown that tumors from MMTV-neu mice expressed high levels of activated JNK1. Levels of this kinase were also highest in Her2/neu overexpressing human breast cancer cell lines. JNK1 inhibition specifically induced apoptosis in these lines. A JNK1 inhibitor also increased the latency period and decreased growth of MMTV-neu tumors by induction of apoptosis. JNK1 was preferentially activated in human breast cancer tissue overexpressing Her2/neu. CONCLUSION: JNK1 promotes cell survival in Her2/neu-positive breast cancer.