Genistein: A Potent Anti-Breast Cancer Agent (original) (raw)
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Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1996
Genistein is a naturally occurring dietary protein tyrosine kinase (PTK) inhibitor that is hypothesized to be responsible for the lower rate of breast cancer observed in Asian women consuming soy. Although genistein is a potent in vitro PTK inhibitor, its mechanism of action in vivo is not known. In vivo, breast cancer growth is regulated by estrogens and peptide growth factors, such as epidermal growth factor (EGF), the receptor of which has intrinsic PTK activity. Therefore, genistein may block mammary epithelial cell growth by interfering with signal transduction events stimulated by estradiol or growth factors. The effect of genistein, related isoflavones, and other tyrosine kinase inhibitors on fetal bovine serum-, estradiol-, and EGF-stimulated cell growth and signal transduction pathways was examined in five human breast cancer cell lines. Genistein inhibited the growth of these cells by each of the growth stimuli with IC50 values ranging from 2.6 to over 20 micrograms/ml. Gr...
Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances
Frontiers in Pharmacology
Background: Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4′,5,7-trihydroxyisoflavone. Genistein has drawn attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects. Objective: The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models. Data sources: English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment, in vivo, in vitro, and clinical studies. Study selection: Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses. Data extraction: Four authors independently carried out the extraction of articles. Data synthesis: One hundred one papers were found suitable for use in this review. Conclusion: This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.
Pleotropic effects of genistein on MCF-7 breast cancer cells
International Journal of Molecular Medicine, 2003
The possible growth inhibitory properties of isoflavones extract of legume sprouts on anticancer activity was measured in human breast cancer cells (MCF-7) using MTT assay and compared with isoflavones of soy beans sprouts in vitro. HPLC analysis of legume sprouts revealed the presence of daidzein and genistein as the predominant isoflavones in Cajanus cajan (Pigeon pea), Cicer arietinum (Chick pea), Glycine max (Soybean), Macrotyloma uniflorum (Horse gram), Lens culinaris (Lentil) and Pisum sativum (Garden pea). The most abundant isoflavone in the legume sprouts was found as genistein followed by daidzein. MTT assay demonstrated the dose dependent inhibition activities of daidzein and genistein on MCF-7 breast cancer cells. Lower concentrations of the extract did not exert a significant effect on cell growth inhibition and cell proliferation inhibition was more at higher concentrations of the extracts. G. max has recorded significant IC value against MCF-7 breast cancer cells followed by M. uniflorum and C. arietinum. The results depicted 50 the use of other legumes especially M. uniflorum and C. arietinum at their sprouts stage for preventing breast cancer apart from the commonly used G. max products.
Breast cancer (BC) is the most common type of cancer in both men and women alike, but it is more prevalent in women. Natural compounds that can modulate the oncogenic process can be considered a significant anti-cancer agent for treating BC. These natural compounds are more effective than synthetic drugs, which have profound side effects on the normal cell and resistance to cancer cells. Genistein is a type of dietary phytoestrogen included in the flavonoid group with a similar structure of estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutics drugs. Several research studies demonstrated that it can target the estrogen receptor (ER), Human epidermal growth factor receptor-2 (HER2), and Breast cancer gene-1 (BRCA-1) in multiple BC cell lines, as well as sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. Genistein effectively showed anti-cancer activities through apoptosis induction, arrest...
Genistein and Cancer: Current Status, Challenges, and Future Directions
Advances in nutrition (Bethesda, Md.), 2015
Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell ...
Processes, 2022
Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer side effects on normal cells. Therefore, we aimed to unravel and analyze several molecular mechanisms of genistein (GNT) against BC. GNT is a type of dietary phytoestrogen included in the flavonoid group with a similar structure to estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutic drugs. Previous research reported that GNT could target the estrogen receptor (ER) human epidermal growth factor receptor-2 (HER2) and several signaling molecules against multiple BC cell lines and sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. More specifically, GNT mediates the anticancer mechanism through apoptos...
Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein
Oncogene, 1999
Breast cancer is the most common cancer among American women, whereas Asian women, who consume a traditional diet high in soy products, have a relatively low incidence. Genistein is a prominent iso¯avonoid in soy products and has been proposed as the agent responsible for lowering the rate of breast cancer in Asian women. We investigated the eects of genistein on cell growth and apoptosis-related gene expression in breast cancer cells MDA-MB-231. We found upregulation of Bax and p21 WAF1 expressions and downregulation of Bcl-2 and p53 expression in genisteintreated cells. Furthermore, DNA ladder formation, CPP32 activation, and PARP cleavage were observed after treatment with genistein, indicating apoptotic cell deaths. Flow cytometry with 7-amino actinomycin D staining showed that the number of apoptotic cells increased with longer treatment of genistein. From these results, we conclude that genistein inhibits the growth of MDA-MB-231 breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through a p53-independent pathway. The up-regulation of Bax and p21 WAF1 may be the molecular mechanisms by which genistein induces apoptosis, however, further de®nitive studies are needed. These results suggest that genistein may be a potentially eective chemopreventive or therapeutic agent against breast cancer.
Effect of genistein on in vitro and in vivo models of cancer
The Journal of nutrition, 1995
In two-thirds of studies on the effect of genistein-containing soy materials in animal models of cancer, the risk of cancer (incidence, latency or tumor number) was significantly reduced. In addition, purified genistein delayed mammary tumor appearance in association with increased cell differentiation in mammary tissue in rats treated with 7, 12-dimethylbenz[a]anthracene when administered neonatally, inhibited phorbol ester-induced H2O2 production in a model of skin cancer, and inhibited aberrant crypt formation in a model of colonic cancer. In in vitro models, genistein inhibited the proliferation of human tumor cell lines in culture with a wide variation in IC50 values (2.6-79 mumol/L, or 1-30 micrograms/mL). In only a few cases was the IC50 below 13.2 mumol/L (5 micrograms/mL), the presumed upper limit for the serum genistein concentration in those on a high soy diet. In future studies, greater emphasis should be placed on the effect of genistein on nontransformed, normal cell l...
Nutrients, 2021
Consumption of dietary natural components such as genistein (GE) found in soy-rich sources is strongly associated with a lower risk of breast cancer. However, bioactive dietary component-based therapeutic strategies are largely understudied in breast cancer treatment. Our investigation sought to elucidate the potential mechanisms linking bioactive dietary GE to its breast cancer chemotherapeutic potential in a special subtype of aggressive breast cancer—triple-negative breast cancer (TNBC)—by utilizing two preclinical patient-derived xenograft (PDX) orthotopic mouse models: BCM-3204 and TM00091. Our study revealed that administration of GE resulted in a delay of tumor growth in both PDX models. With transcriptomics analyses in TNBC tumors isolated from BCM-3204 PDXs, we found that dietary soybean GE significantly influenced multiple tumor-regulated gene expressions. Further validation assessment of six candidate differentially expressed genes (DEGs)—Cd74, Lpl, Ifi44, Fzd9, Sat1 and ...