Elsevier

Advances in Nutrition

Volume 6, Issue 4, July 2015, Pages 408-419
Advances in Nutrition

Genistein and Cancer: Current Status, Challenges, and Future Directions

https://doi.org/10.3945/an.114.008052 Get rights and content
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ABSTRACT

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 cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)–associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.

genistein
cancer
source
bioavailability
safety

Abbreviations

ABCG2
ATP-binding cassette subfamily G member 2
AP-1
activator protein 1
ATO
arsenic trioxide
ATR
ataxia telangiectasia and Rad3-related kinase
Bax
Bcl-2–associated X protein
Bcl-2
B cell lymphoma 2
BRCA
breast cancer growth suppressor protein
Cdc2/Cdk1
cell division cycle protein 2 homolog/cyclin-dependent kinase 1
Cdc25B
cell division cycle 25B
CENPF
centromere protein F
COX-2
cyclooxygenase 2
CYP
cytochrome P450
dFMGEN
7-difluoromethyl-5,4′-dimethoxygenistein
DKK1
Dickkopf-related protein 1
EGFR
epidermal growth factor receptor
ER
estrogen receptor
ERK
extracellular signal-regulated kinase
FoxM1
Forkhead box protein M1
GCSC
gastric cancer stem cell
Gli1
glioma-associated oncogene family zinc finger 1
GST
glutathione S-transferase
HCC
hepatocellular carcinoma cell
IFS
isoflavone synthase
INT-1
integration 1
IκB
inhibitor of NF-κB
KIF
kinesin-like protein
MMP-9
matrix metalloproteinase 9
PCNA
proliferating cell nuclear antigen
PI3K/Akt
phosphoinositide 3 kinase/Akt
PTEN
phosphatase and tensin homolog
SCLC
small cell lung cancer
THIF
5,7,3′,4′ tetrahydroxyisoflavone
TNFR-1
tumor necrosis factor receptor 1
TRAIL
tumor necrosis factor–related apoptosis-inducing ligand
TSA
trichostatin A
UGT
UDP-glucuronosyltransferase
Wnt/β-catenin
Wingless and integration 1 β-catenin

Cited by (0)

A Sureda was supported by CIBEROBN (CB12/03/30038).

Author disclosures: C Spagnuolo, GL Russo, IE Orhan, S Habtemariam, M Daglia, A Sureda, SF Nabavi, KP Devi, MR Loizzo, R Tundis, and SM Nabavi, no conflicts of interest.