A Review of Promising Natural Chemopreventive Agents for Head and Neck Cancer

Abstract

Head and neck squamous cell carcinoma (HNSCC) accounts for 300,000 deaths per year worldwide, and overall survival rates have shown little improvement over the past three decades. Current treatment methods including surgery, chemotherapy, and radiotherapy leave patients with secondary morbidities. Thus, treatment of HNSCC may benefit from exploration of natural compounds as chemopreventive agents. With excellent safety profiles, reduced toxicities, antioxidant properties, and general acceptance for use as dietary supplements, natural compounds are viewed as a desirable area of investigation for chemoprevention. Though most of the field is early in development, numerous studies display the potential utility of natural compounds against HNSCC. These compounds face additional challenges such as low bioavailability for systemic delivery, potential toxicities when consumed in pharmacologic doses, and acquired resistance. However, novel delivery vehicles and synthetic analogues have shown to overcome some of these challenges. This review covers 11 promising natural compounds in the chemoprevention of HNSCC including vitamin A, curcumin, isothiocyanate, green tea, luteolin, resveratrol, genistein, lycopene, bitter melon, withaferin A, and guggulsterone. The review discusses the therapeutic potential and associated challenges of these agents in the chemopreventive efforts against HNSCC. Cancer Prev Res; 11(8); 441-50. ©2018 AACR.

Figure 1

The schematic represents various signaling pathways that occur within tumor cells, which allow for cell growth, proliferation, and invasion. The arrows between the signaling molecules represent progressions in the pathway. For example, IGFR signals through the JAK/STAT3 pathway to allow for cell proliferation. The natural compounds discussed can promote cell apoptosis (Luteolin, Resveratrol) and/or inhibit cell growth, proliferation, and invasion (Luteolin, Resveratrol, Genistein, GTE, Curcumin, ITCs, Lycopene). IGFR = Insulin-like growth factor 1 receptor; JAK1 = Janus kinase 1; STAT3 = signal transducer and activator of transcription 3; EGFR = epidermal growth factor receptor; PI3K = phosphatidylinositol-4,5-bisphosphate 3-kinase; AKT = protein kinase B; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; VEGFR = receptors for vascular endothelial growth factors ; MAPK = mitogen-activated protein kinases; VEGF = vascular endothelial growth factor; p53 = tumor protein p53; p21 = cyclin-dependent kinase inhibitor 1; CDK4/6 = cyclin-dependent kinase 4/6; Rb = retinoblastoma protein; E2F = transcription factor coder for eukaryotes; MMPS = matrix metalloproteinases.

Figure 2

The figure shows the various signaling pathways affected by curcumin. The molecule can act to inhibit a number of pathways that allow for tumor growth and invasion. Curcumin can also lead to upregulation of molecules that lead to cell cycle arrest in tumor cells. EGFR = epidermal growth factor receptor; VEGFR = receptors for vascular endothelial growth factors; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK = mitogen-activated protein kinases; p53 = tumor protein p53; p21 = cyclin-dependent kinase inhibitor 1