Sustained release of melatonin: A novel approach in elevating efficacy of tamoxifen in breast cancer treatment.

Abstract

Finding advanced anti-cancer agents with selective toxicity in tumor tissues is the goal of anticancer delivery systems. This study investigated potential application of nanostructured lipid carriers (NLCs) in increasing melatonin induced cytotoxicity and apoptosis in MCF-7 breast cancer cells.Melatonin-loaded NLCs were characterized for particle size, zeta potential, Fourier transforms infrared spectroscopy, differential scanning calorimetry, cellular uptake, and scanning electron microscope (SEM). Anti-proliferative and apoptotic effects of new formulation were evaluated by MTT and flow cytometric assays, respectively. Gene expression of apoptotic markers including survivin, Bcl-2 and Bid were examined by Real time quantitative PCR.The optimized formulation of NLCs revealed mean particle size of 71آ±5nm with nearly narrow size distribution. The formulation exhibited an acceptable stability during four months in terms of size and lack of drug release. The IC50 values for melatonin and tamoxifen were 1.3آ±0.4mM and 30.7آ±5.2?M, respectively. Melatonin loaded NLCs decreased percentage of cell proliferation from 55آ±7.2% to 40آ±4.1% (p<0.05). Co-treatment of the cells with melatonin loaded nanoparticles and tamoxifen caused two fold increase in the percentage of apoptosis (p<0.05). Evaluation of gene expression profile demonstrated a marked decrease in anti-apoptotic survivin with increase in pro-apoptotic Bid mRNA levels.Taken together, our results suggest NLC technology as a promising delivery system, which elevates the efficacy of chemotherapeutics in breast cancer cells.