title: Sustained release of melatonin: A novel approach in elevating efficacy of tamoxifen in breast cancer treatment.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  The optimized formulation of NLCs revealed mean particle size of 71±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 1.3±0.4mM and 30.7±5.2μM, respectively. Melatonin loaded NLCs decreased percentage of cell proliferation from 55±7.2% to 40±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.
  
  
  CONCLUSIONS
  Taken together, our results suggest NLC technology as a promising delivery system, which elevates the efficacy of chemotherapeutics in breast cancer cells.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sabzichi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nsamadi@ualberta.ca.
authors.forename: Nasser
authors.initials: N
authors.lastname: Samadi
authors.affiliation: Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Mohammadian
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.affiliation: Umbilical Cord Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Akbarzadeh
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ommoleila
authors.initials: O
authors.lastname: Molavi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008550:Melatonin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D013629:Tamoxifen; D008550:Melatonin
keywords: Apoptosis; MCF-7; Melatonin; Nano structured lipid carrier (NLC); Tamoxifen