Cancer and Metastasis Reviews

, Volume 31, Issue 1–2, pp 323–351 | Cite as

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities

NON-THEMATIC REVIEW

Abstract

Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate, and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin, apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin, daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell–cell attachment, tissue-barrier degradation, migration, invasion, cell–matrix adhesion, and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on anti-angiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.

Keywords

Angiogenesis Chemoprevention Flavonoid Invasion Metastasis 

Abbreviations

Ang

Angiopoietin

AOM

Azoxymethane

CXCR4

CXC chemokine receptor 4

COX-2

Cyclooxygenase-2

ECM

Extracellular matrix

EGCG

(−)-Epigallocatechin-3-gallate

EGFR

Epidermal growth factor receptor

EMMPRIN

Extracellular matrix metalloproteinase inducer

EMT

Epithelial–mesenchymal transition

ER

Estrogen receptor

ErbB2

Epidermal growth factor receptor-related protein B2

FAK

Focal adhesion kinase

FOXO3

Forkhead box O3

HGF

Hepatocyte growth factor

HIF

Hypoxia-inducible factor

HRG

Heregulin-β1

HSP

Heat shock protein

HUVECs

Human umbilical vein endothelial cells

iNOS

Inducible nitric oxide synthase

KAI1

Kangai-1

LLC

Lewis lung carcinoma

MAPKAPK2

MAP kinase-activated protein kinase 2

mdm2

Murine double minute 2

MET

Mesenchymal–epithelial transition

MMP

Matrix metalloproteinases

MT-1 MMP

Membrane type-1 MMP

MTA3

Metastasis-associated protein 3

MUC1

Mucin 1, cell surface-associated

OPG

Osteoprotegerin

OPN

Osteopontin

PAI

Plasminogen activator inhibitor

PECAM

Platelet endothelial cell adhesion molecule

PMA

Phorbol 12-myristate 13-acetate

PKC

Protein kinase C

PGE2

Prostaglandin E2

PMN

Polymorphonuclear phagocytes

PN-II

Protease nexin-II

PSA

Prostate-specific antigen

RANKL

Receptor activator of nuclear factor-kB ligand

RECK

Reversion-inducing cysteine-rich protein with kazal motifs

SLUG

Zinc finger protein SNAI2

TIMP

Tissue inhibitor metalloproteinase protein

TRAMP

Transgenic adenocarcinoma of mouse prostate

uPA

Urokinase plasminogen activator

uPAR

Urokinase plasminogen activator receptor

VASP

Vasodilator-stimulated phosphoprotein

VEGF

Vascular endothelial growth factor

ZEB1

Zinc finger E-box-binding homeobox 1

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Graduate Institute of Applied Science of LivingTainan University of TechnologyTainan CityTaiwan
  2. 2.Department of Food Science and BiotechnologyNational Chung Hsing UniversityTaichungTaiwan

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