Genistein, a Potential Phytochemical against Breast Cancer Treatment-Insight into the Molecular Mechanisms
Open Access
Abstract
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 apoptosis induction, arresting the cell cycle, inhibiting angiogenesis and metastasis, mammosphere formation, and targeting and suppressing tumor growth factors. Furthermore, it acts via upregulating tumor suppressor genes and downregulating oncogenes in vitro and animal model studies. In addition, this phytochemical synergistically reverses the resistance mechanism of standard chemotherapeutic drugs, increasing their efficacy against BC. Overall, in this review, we discuss several molecular interactions of GNT with numerous cellular targets in the BC model and show its anticancer activities alone and synergistically. We conclude that GNT can have favorable therapeutic advantages when standard drugs are not available in the pharma markets.Keywords
Funding Information
- National Research Foundation of Korea (NRF-2020R1I1A2066868)
This publication has 159 references indexed in Scilit:
- Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cellsBMC Complementary and Alternative Medicine, 2014
- Epigenetic Regulation of Multiple Tumor-Related Genes Leads to Suppression of Breast Tumorigenesis by Dietary GenisteinPLOS ONE, 2013
- Epigenetic reactivation of estrogen receptor-α (ERα) by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancerMolecular Cancer, 2013
- The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in TherapyChemotherapy Research and Practice, 2012
- Soy Isoflavone Supplementation for Breast Cancer Risk Reduction: A Randomized Phase II TrialCancer Prevention Research, 2012
- Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activityBMC Cancer, 2011
- Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomesReproductive Toxicology, 2011
- Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen GenisteinMolecular & Cellular Proteomics, 2011
- Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC–MS/MS method: Application to an oral bioavailability study of genistein in miceJournal of Pharmaceutical and Biomedical Analysis, 2010
- Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor‐positive and HER2‐overexpressing human breast cancer cellsMolecular Carcinogenesis, 2007