Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis

Abstract

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic.

Myricetin suppresses breast cancer metastasis through down‐regulating the activity of matrix metalloproteinase (MMP)‐2/9

“…MMPs play an important role during multiple stages of tumour progression such as growth, angiogenesis, and migration based on their abilities in ECM degradation and tissue remodeling. We have made a further summary of the roles of MMPs in breast cancer metastasis (Ci et al, ). Cell migration and invasion are closely associated with the enhanced activation of MMP‐2 and MMP‐9.…”

“…After treatment with myricetin for 24 and 48 hr, cell adhesion, cell migration, as well as cell invasion ability were significantly sup- abilities in ECM degradation and tissue remodeling. We have made a further summary of the roles of MMPs in breast cancer metastasis (Ci et al, 2016). Cell migration and invasion are closely associated with the enhanced activation of MMP-2 and MMP-9.…”

The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective

“…VEGF and VEGF‐receptors are key players in the regulation of vascular cell development and are also involved in monocyte regulation, macrophage migration, angiogenesis, and vascular permeability (Alvarez‐Aznar, Muhl, & Gaengel, ), nerve regeneration, and attenuating vascular complications associated with diabetes (Suganya, Bhakkiyalakshmi, Sarada, & Ramkumar, ). Interference with the VEGF‐signaling pathway has been proposed as a mechanism behind flavonoids’ anticancer activity (Ci, Qiao, & Han, ) and VEGF is a suggested risk marker for coronary heart disease (Wang et al., ). Quercetin and cocoa flavonoids have also been reported to act on VEGF (Donnini, Finetti, Lusini, & Morbidelli, ; Kim et al., ), providing further evidence that VEGF is a reasonable mechanistic target.…”

Breast cancer lung metastasis: Molecular biology and therapeutic implications

“…However, the 5-y overall survival rate of metastatic breast cancer is less than 30%. 161 Despite available therapies for metastatic breast cancer, such as cytotoxic chemotherapies, endocrine therapies, and targeted therapies, survival rate is still low. This may be secondary to the lower response rate to systemic chemotherapy and stronger therapeutic resistance of metastatic breast cancer.…”