Therapeutic potential of curcumin and its nanoformulations for treating oral cancer

Abstract

The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality. Oral cancer is the most common cancer in the head and neck region, and is predominantly of epithelial origin (i.e. squamous cell carcinoma). Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy. Though proven effective, chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence. Thus, there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer. Among the available adjuvant therapies is curcumin, a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa. Curcumin has been demonstrated to have anti-infectious, antioxidant, anti-inflammatory, and anticarcinogenic properties. Curcumin has poor bioavailability, which has been overcome by its various analogues and nanoformulations, such as nanoparticles, liposome complexes, micelles, and phospholipid complexes. Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets, including activator protein 1, protein kinase B (Akt), nuclear factor κ-light-chain-enhancer of activated B cells, mitogen-activated protein kinase, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways. These targets play important roles in oral cancer pathogenesis, thereby making curcumin a promising adjuvant treatment modality. This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.

Keywords: Oral cancer, Oral squamous cell carcinoma, Analogues, Curcumin, Adjuvant therapy, Nanocurcumin, Curcumin nanoformulations, Curcumin analogues

Core Tip: Oral cancer has a high disease burden worldwide. Oral squamous cell carcinoma is the most predominant subtype of oral cancer. The majority of oral cancers present at an advanced stage and are associated with a poor prognosis. Timely diagnosis and early treatment are critical to achieve a superior outcome. Surgery is the recommended treatment for oral cancer; other treatment modalities are radiotherapy with or without chemotherapy. Curcumin, a plant derivative, is one among the available adjuvant therapies that has been studied for its anticarcinogenic potential in the setting of various cancers. Curcumin has been proven to modulate intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis, and cell death, with evidence supporting its use in cancer therapy. This review aims to summarize the molecular pathways involved in oral carcinoma pathogenesis, to explore different therapeutic interactions of curcumin, and to highlight the role of novel curcumin formulations in oral cancer treatment.