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

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.

Use of Polyphenolic Compounds in Dermatologic Oncology

“…Since resveratrol can cause DNA damage to squamous cell carcinoma in the head and neck area [202], causing p53-dependent apoptosis [203], and inhibiting accumulation of hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF) expression [204], resveratrol can be used as either a chemopreventive agent [205, 206] or a therapeutic one, improving cytotoxic irradiation-based therapy, by decreasing cyclin B, cyclin D, CDK2, CDK4, and the anti-apoptotic molecule Fas-associated protein with death domain-like IL-1β-converting enzyme-inhibitory protein (FLIP), Bcl-2, and SVV [178, 207–209]. Resveratrol may also improve the cytotoxicity of 5-fluorouracil [210, 211] (Table 1; Fig.…”

Assessing the aftermath of an alcohol‐fueled weekend: Alcohol‐induced DNA damage and faulty repairs may raise the risk of certain cancers, but resveratrol could provide some relief

“…The accumulating evidence suggests that resveratrol targets and kills cells that cannot repair their own damaged DNA, thereby preventing them from becoming cancerous . At the molecular level, studies have indicated that resveratrol targets the protein DNA polymerase.…”

Cytoprotective effects of (E)-N-(2-(3, 5-dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) against 4-nitroquinoline 1-oxide-induced damage in CCD-18Co human colon fibroblast cells

“…The cancer chemoprevention approach exploits nontoxic natural or synthetic pharmacological agents to prevent, block or reverse the multistep processes of carcinogenesis [9,10]. Chemopreventive agents inhibit the invasive development of cancer by affecting the three defined stages of carcinogenesis namely initiation, promotion and progression which are induced by carcinogens through genetic and epigenetic mechanisms [11,12].…”