Anti-Cancer Activity of the Curcumin Analog Mono-O-Demethylcurcumin on Invasive Multidrug-Resistant Oral Squamous Cell Carcinoma in vitro

Abstract

Metasrasis is a major cause of death in cancer patients. Oral squamous cell carcinoma is the most common head and neck cancer, characterized by a poor prognosis and low survival rate. The average five-year survival rates vary from 50 to 80%, according to the occurrence of invasion and metastasis, which is responsible for determining the stage of the cancer. Curcuminoid is the major curcuminoid compound isolated from turmeric and has been reported to have excellent anti-cancer activity in various tumors in both in vitro and in vivo models. This study aimed to investigate the anti-cancer activity of the curcumin analog mono-O-demethylcurcumin compared with curcumin, in an invasive multidrug-resistant oral squamous cell carcinoma cell line (CLS0354/DX). The anti-proliferation effect was determined by tetrazolium dye MTT assay. The anti-migration and anti-invasion effects were investigated by the transwell migrayion and invasion chamber assay, respectively. The results showed that both compounds reduces CLS-354/DX viability and migration and invasion ability, but mono-O-demethylcurcumin was significantly more potent than curcumin. The half maximal inhibitory concentration (IC[subscript 50]) values of curcumin and mono-O-demethylcurcumin were 44.99+-2.92 uM and 19.10+-0.71 Um, respectively. Application of mono-O-demethylcurcumin and curcumin at non-cytotoxic concentrations inhibited cell migration and invasion in a dose-dependent manner. Treatment with 5 uM mono-O-demethylcurcumin decreased CLS-354/DX migration and invasion scores by 63.84+-3.31 % and 11.40+-2.82% respectively. While, treatment with 15 uM of curcumin showed increased CLS-354/DX migration and invasion scores by 72.45+-4.17% and 21.70+- 4.39%, respectively. These results suggest that mono-O-demethylcurcumin exhibits excellent anti-proliferation, anti-migration and anti-invasion activity on multidrug-resistant oral squamous cell carcinoma. This compound may thus have a potential as a chemopreventative or therapeutic agent for multidrug-resistant oral cancer.