stilbenes and Fibrocystic-Breast-Disease

The phytoalexin, trans-resveratrol (RES), is a polyphenolic compound found in plants and fruits that seems to have a wide spectrum of biological activities. It has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumor initiation, promotion, and progression. RES is also a phytoestrogen, which binds to and activates estrogen receptors (ERs) that regulate the transcription of estrogen-responsive target genes. We used two human breast tumor cell lines (MCF7 and MBA-MB-231) and one fibrocystic breast cell line (MCF10a) to examine whether RES altered mRNA expression of genes that are involved in biological pathway frequently altered during carcinogenesis. Two GEarray systems were used to screen the differentially expressed genes between RES-treated cells and control cells. The differentially expressed genes were analyzed further by quantitative reverse transcriptase polymerase chain reaction. Here, we demonstrate that RES regulates mRNA expression of several genes involved in cell cycle control, apoptosis, metastasis, cell-cell adhesion, and ER signaling pathway. This effect of RES on the gene expression appears in correlation with chemoprevention activities of RES described previously. RES is also found to be more active in ER+ than ER- cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Adhesion; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Fibrocystic Breast Disease; Gene Expression Regulation, Neoplastic; Humans; Receptors, Estrogen; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes; Transcription, Genetic

trans-Resveratrol, or 3,5,4'trihydroxy-trans-stilbene, is a polyphenolic compound that seems to provide a protective effect against several types of cancer, notably breast cancer. Through its phytoestrogenic properties it regulates the expression of hormone-dependent genes, such as the oncosuppressor BRCA1, in breast cells. This gene is involved in the majority of hereditary breast cancer, as well as sporadic cancers.. We used three human breast tumor cell lines (HBL100, MCF7 and MBA-MB-231) and one breast cell line (MCF10a) derived from a fibrocystic disease to study in vitro the effect of resveratrol on the transcription of a group of genes whose proteins interact in different pathways with BRCA1. BRCA1, BRCA2, ER alpha, ER beta, p53, p21(waf1/cip1), CBP/P300, RAD51, pS2 and Ki67 mRNA were quantified using real-time quantitative RT-PCR with an ABI 7700 apparatus.. Resveratrol modulated the expression of these genes in a pattern dependent on the status of alpha and beta estrogen receptors. These results show that resveratrol regulates gene expression via the estrogen receptor pathway and also an undetermined pathway.. Thus, resveratrol seems to have an effect on breast tumor cell lines, on a fibrocystic cell line by affecting several factors regulating the function of BRCA1.

Topics: Antineoplastic Agents, Phytogenic; BRCA1 Protein; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Fibrocystic Breast Disease; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Receptors, Estrogen; Resveratrol; Stilbenes; Transcription, Genetic; Tumor Suppressor Proteins