A Perspective on Chemoprevention by Resveratrol in Head and Neck Squamous Cell Carcinoma

  • Sangeeta Shrotriya
  • Rajesh Agarwal
  • Robert A. Sclafani
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 815)

Abstract

Head and neck squamous cell carcinoma (HNSCC) accounts for around 6 % of all cancers in the USA. Few of the greatest obstacles in HNSCC include development of secondary primary tumor, resistance and toxicity associated with the conventional treatments, together decreasing the overall 5-year survival rate in HNSCC patients to ≤50 %. Radiation and chemotherapy are the conventional treatment options available for HNSCC patients at both early and late stage of this cancer type malignancy. Unfortunately, patients response poorly to these therapies leading to relapsed cases, which further, emphasizes the need of additional strategies for the prevention/intervention of both primary and the secondary primary tumors post-HNSCC therapy. In recent years, growing interest has focused on the use of natural products or their analogs to reduce the incidence and mortality of cancer, leading to encouraging results. Resveratrol, a component from grape skin, is one of the well-studied agents with a potential role in cancer chemoprevention and other health benefits. As an anticancer agent, resveratrol suppresses metabolic activation of pro-carcinogens to carcinogens by modulating the metabolic enzymes responsible for their activation, and induces phase II enzymes, thus, further detoxifying the effect of pro-carcinogens. Resveratrol also inhibits cell growth and induces cell death in cancer cells by targeting cell survival and cell death regulatory pathways. Growing evidence also suggest that resveratrol directly binds to DNA and RNA, activates antioxidant enzymes, prevents inflammation, and stimulates DNA damage checkpoint kinases affecting genomic integrity more specifically in malignant cells.

Abbreviations

4NQO

4-Nitroquinoline 1-oxide

ADH

Alcohol dehydrogenase

ALDH

Aldehyde dehydrogenase

AP-1

Activator protein 1

ARE

Antioxidant response element

ATM

Ataxia telangiectasia mutated

ATR

Ataxia telangiectasia-Rad3-related

B[A]P

Benzo[a]pyrene

BER

Base excision repair

Brca1

Breast cancer gene 1

Cdc25C

Cell division cycle 25C

CDKs

Cyclin dependent kinases

Chk1/2

Checkpoint kinase 1/2

COX2

Cyclooxygenase 2

CYP450

Cytochrome P450s

DMBA

7,12-Dimethylbenz[α]anthracene

DSBs

Double strand break

EGFR

Epidermal growth factor receptor

Egr 1

Early growth response 1

EMT

Epithelial mesenchymal transition

FA

Fanconi anemia

GSH

Glutathione

HNSCC

Head and neck squamous cell carcinoma

HPV

Human papilloma virus

HRR

Homologous recombination repair

IGFR

Insulin-like growth factor receptor

iNOS

Inducible nitric oxide synthetase

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinases

MCM

Minichromosome maintenance

MMPs

Metalloproteinases

MMR

Mismatch repair

mTOR

Mammalian target of rapamycin

NER

Nucleotide excision repair

NF-kB

Nuclear factor kappa B

NHEJ

Non-homologous end joining

NNK

4-Methylnitrosamine-1-(3-pyridyl)-1-butanone

P53

Protein 53

PARP

Poly (ADP-ribose) polymerases

PCNA

Proliferating cell nuclear antigen

RA

Retinoic acid

Rb

Retinoblastoma protein

Res

Resveratrol

ROS/RNS

Reactive oxygen species/reactive nitrogen species

SPT

Secondary primary tumor

SSBs

Single strand break

STAT3

Signal transducer and activator of transcription 3

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Sangeeta Shrotriya
    • 1
  • Rajesh Agarwal
    • 1
    • 2
  • Robert A. Sclafani
    • 2
    • 3
  1. 1.Department of Pharmaceutical SciencesUniversity of Colorado DenverAuroraUSA
  2. 2.University of Colorado Cancer Center, University of Colorado DenverAuroraUSA
  3. 3.Department of Biochemistry and Molecular GeneticsUniversity of Colorado DenverAuroraUSA

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