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

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.

Keywords

  • Human Papilloma Virus
  • Fanconi Anemia
  • Ataxia Telangiectasia Mutate
  • Apoptosis Ligand
  • Alcohol Metabolism

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Fig. 19.1

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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Supported by grants to R. Sclafani from the Fanconi Anemia Research Foundation and the University of Colorado Cancer Center.

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Shrotriya, S., Agarwal, R., Sclafani, R.A. (2015). A Perspective on Chemoprevention by Resveratrol in Head and Neck Squamous Cell Carcinoma. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_19

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