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Current Pharmacology Reports

, Volume 3, Issue 6, pp 423–446 | Cite as

Plant Flavone Apigenin: an Emerging Anticancer Agent

  • Eswar Shankar
  • Aditi Goel
  • Karishma Gupta
  • Sanjay GuptaEmail author
Cancer Chemoprevention (R Agarwal, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cancer Chemoprevention

Abstract

Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4′,5,7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retains potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in the liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

Keywords

Cancer chemoprevention Dietary agents Plant flavonoids Health effects Nanoparticle Polyphenols 

Abbreviations

4-HPR

N-(4-Hydroxyphenyl) retinamide

5-FU

Fluorouracil

ACF

Aberrant crypt foci

ADM

Doxorubicin

ADP

Adenosine di-phosphate

AICR

American Institute for Cancer Research

AOM

Azoxymethane

APC

Adenomatous polyposis coli

ATF3

Activating transcription factor 3

BCRP

Breast cancer resistance protein

CK2

Casein kinase 2

COX-2

Cyclooxygenase-2

DISC

Death-inducing signaling complex

DOX

Doxorubicin

DR4

Death receptor 4

EGFR

Epidermal growth factor receptor

ERK

Extracellular regulated kinase

FAK

Focal adhesion kinase

GADD45

DNA fragmentation factor-45

Gli1

Glioma-associated oncogene 1

GLUT1

Glucose transporter 1

GSTA1

Glutathione S-transferase A1

HDAC

Histone deacetylase

HIF-1α

Hypoxia-inducible factor 1-alpha

hTERT

Telomerase reverse transcriptase

ICAM-1

Intercellular adhesion molecule-1

IFNAR1

Type I interferon receptor 1

IFN-γ

Interferon gamma

IGF

Insulin-like growth factor

IL6

Interleukin-6

JAK

Janus kinase

JNK

c-Jun amino-terminal kinase

KLF4

Krüpple-like factor 4

MAPK

Mitogen-activated protein kinases

MMP

Matrix metalloproteinases

NADPH

Nicotinamide adenine dinucleotide phosphate

NF-ĸB

Nuclear factor-kappaB

NIS

Na+/I− symporter

NSCLC

Non-small cell lung cancer

ODC

Ornithine decarboxylase

PARP

Poly (ADP-ribose) polymerase

PD-L1

Programmed death-ligand 1

PDPK FA

Proline-directed protein kinase FA

PI3K

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PKC

Protein kinase C

PLGA

Poly-lactic-co-glycolide

PMA

Protein kinase C-activating phorbol ester

ROS

Reactive oxygen species

SOD

Superoxide dismutase

Stat

Signal transducer and activator of transcription

TGF-β

Transforming growth factor-beta

TRAIL

Tumor necrosis factor-related apoptosis-inducing ligands

TRAMP

Transgenic adenocarcinoma of the mouse prostate

UGT1A1

UDP-glucuronosyltransferase 1–1

VEGF

Vascular endothelial growth factor

WCRF

World Cancer Research Fund

Notes

Acknowledgements

We sincerely apologize to those investigators whose work could not be cited due to space constraints.

Funding information

The original work from author’s laboratory outlined in this review was supported by VA Merit Review 1I01BX002494; United States Public Health Service Grants RO1CA108512, R21CA193080, and R03CA186179 and Department of Defense grant W81XWH-15-1-0558 to SG.

Compliance with Ethical Standards

Conflict of Interest

The authors have no competing interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Urology, The James and Eilleen Dicke LaboratoryCase Western Reserve UniversityClevelandUSA
  2. 2.Department of Urology, The Urology InstituteUniversity Hospitals Cleveland Medical CenterClevelandUSA
  3. 3.Department of Biology, School of Undergraduate StudiesCase Western Reserve UniversityClevelandUSA
  4. 4.Department of NutritionCase Western Reserve UniversityClevelandUSA
  5. 5.Division of General Medical SciencesCase Comprehensive Cancer CenterClevelandUSA
  6. 6.Department of UrologyLouis Stokes Cleveland Veterans Affairs Medical CenterClevelandUSA

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