The AAPS Journal

, Volume 16, Issue 1, pp 151–163 | Cite as

Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention

  • Vijay S. Thakur
  • Gauri Deb
  • Melissa A. Babcook
  • Sanjay GuptaEmail author
Review Article Theme: Natural Products Drug Discovery in Cancer Prevention


In recent years, “nutri-epigenetics,” which focuses on the influence of dietary agents on epigenetic mechanism(s), has emerged as an exciting novel area in epigenetics research. Targeting of aberrant epigenetic modifications has gained considerable attention in cancer chemoprevention research because, unlike genetic changes, epigenetic alterations are reversible and occur during early carcinogenesis. Aberrant epigenetic mechanisms, such as promoter DNA methylation, histone modifications, and miRNA-mediated post-transcriptional alterations, can silence critical tumor suppressor genes, such as transcription factors, cell cycle regulators, nuclear receptors, signal transducers, and apoptosis-inducing and DNA repair gene products, and ultimately contribute to carcinogenesis. In an effort to identify and develop anticancer agents which cause minimal harm to normal cells while effectively killing cancer cells, a number of naturally occurring phytochemicals in food and medicinal plants have been investigated. This review highlights the potential role of plant-derived phytochemicals in targeting epigenetic alterations that occur during carcinogenesis, by modulating the activity or expression of DNA methyltransferases, histone modifying enzymes, and miRNAs. We present in detail the epigenetic mode of action of various phytochemicals and discuss their potential as safe and clinically useful chemopreventive strategies.


cancer chemoprevention dietary agents DNA methylation epigenetics histone modification microRNA 



v-akt murine thymoma viral oncogene homolog 1


Allyl mercaptan


Activator Protein-1


Androgen receptor


BCL2-associated X protein


B-cell CLL/lymphoma 2


B-cell lymphoma-extra large


B-cell-specific Moloney murine leukemia virus integration site 1


Breast cancer 1, early onset


CREB-binding protein


Cyclin D2


Cell division cycle 25 homolog A


Cyclin-dependent kinase


v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog






Cylindromatosis (turban tumor syndrome)


Diallyl disulfide


Diallyl sulfide


Diallyl trisulfide


Dihydrofolate reductase




DNA methyltransferase


DNA (cytosine-5)-methyltransferase 3-like


E2F transcription factor










Epidermal growth factor receptor


Estrogen receptor


Estrogen receptor beta


Human epidermal growth factor receptor 2


Estrogen receptor alpha


Enhancer of zeste homolog 2


Forkhead box protein O3


SAGA complex histone acetyltransferase catalytic subunit Gcn5


Glutathione-S-transferase pi 1


Histone acetyl transferases


Histone deacetylases


Human epidermal growth factor receptor 2

HIF-1 α

Hypoxia inducible factor 1, alpha subunit


Histone lysine methyltransferases


Human mutL homolog 1

HOX family proteins

Homeobox family proteins


Heat shock protein 90


Human telomerase reverse transcriptase


TNF-induced interferon-gamma-inducible protein 10




Lymphoid enhancer factor


Methylated DNA binding domain proteins


Induced myeloid leukemia cell differentiation protein Mcl-1


Minichromosome maintenance gene


Methylguanine-DNA methyltransferase


Macrophage inflammatory protein 2




Metastasis associated 1 family member 2


Nuclear factor kappa-light-chain-enhancer of activated B cells


Notch homolog 1, translocation-associated (Drosophila)


Organosulfur compounds


Cyclin-dependent kinase 4 inhibitor A


Cyclin-dependent kinase inhibitor 1A


Tumor protein 53


Poly ADP-ribose polymerase


K(lysine) acetyltransferase 2B


Polycomb group proteins


Programmed cell death 4


Phenethyl isothiocyanate


Phosphoribosyl pyrophosphate synthetase 1


Phosphatase and tensin homolog deleted on chromosome 10


Retinoic acid receptor, beta 2




Rat sarcoma transforming oncogene


RAS association domain family 1A

RXR alpha

Retinoid X receptor, alpha




S-adenosyl methionine




Sirtuin (silent mating type information regulation 2 homolog) 1


Solute carrier family 16, member 1


Sorting nexin-19


Transcription Factor Sp1


Transforming growth factor, beta receptor II


Transforming growth factor, beta


Phosphotyrosine picked threonine-protein kinase


Vascular endothelial cell growth factor


Zinc finger and BTB domain containing 10


Zinc finger E-box binding homeobox 1


Zinc finger protein 513



The original work from author’s laboratory outlined in this review was supported by United States Public Health Service Grants RO1CA108512, RO1CA115491 and RO1AT002709. We acknowledge Shyama Prasad Mukherjee (SPM) fellowship provided to GD by the Council of Scientific and Industrial Research (CSIR), India and Fulbright-Nehru Doctoral and Professional Research fellowship provided by United States—India Educational Foundation (USIEF) for her work in the United States. MAB is supported by NIH 5T32DK007316 Ruth L. Kirschstein Pre-Doctoral Fellowship through the Metabolism Training Program. We apologize to those investigators whose original work could not be cited owing to the space limitations.

Conflict of Interest

The authors have no competing interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Vijay S. Thakur
    • 1
  • Gauri Deb
    • 1
    • 2
  • Melissa A. Babcook
    • 1
    • 3
  • Sanjay Gupta
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of UrologyCase Western Reserve University, University Hospitals Case Medical CenterClevelandUSA
  2. 2.Department of BiotechnologyIndian Institute of TechnologyGuwahatiIndia
  3. 3.Department of NutritionCase Western Reserve UniversityClevelandUSA
  4. 4.Division of General Medical SciencesCase Comprehensive Cancer CenterClevelandUSA

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