Therapeutic potential of curcumin and its nanoformulations for treating oral cancer

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 antiinfectious,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 factorκ-light-chainenhancer 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.

Identification of commonly regulated genes in HPV18-and HPV16-infected cervical cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.