Mehdi Sabzichi1, Nasser Samadi2, Jamal Mohammadian3, Hamed Hamishehkar4, Maryam Akbarzadeh5, Ommoleila Molavi6. 1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nsamadi@ualberta.ca. 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Umbilical Cord Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 6. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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. CONCLUSION: Taken together, our results suggest NLC technology as a promising delivery system, which elevates the efficacy of chemotherapeutics in breast cancer cells.
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. CONCLUSION: Taken together, our results suggest NLC technology as a promising delivery system, which elevates the efficacy of chemotherapeutics in breast cancer cells.
Authors: Mahmud Hasan; Mohamed Akmal Marzouk; Saugat Adhikari; Thomas D Wright; Benton P Miller; Margarite D Matossian; Steven Elliott; Maryl Wright; Madlin Alzoubi; Bridgette M Collins-Burow; Matthew E Burow; Ulrike Holzgrabe; Darius P Zlotos; Robert E Stratford; Paula A Witt-Enderby Journal: Mol Pharmacol Date: 2019-06-20 Impact factor: 4.436
Authors: B Farhood; N H Goradel; K Mortezaee; N Khanlarkhani; E Salehi; M S Nashtaei; H Mirtavoos-Mahyari; E Motevaseli; D Shabeeb; A E Musa; M Najafi Journal: Clin Transl Oncol Date: 2018-08-22 Impact factor: 3.405
Authors: Hadi Chavoshi; Vahid Vahedian; Somaiyeh Saghaei; Mohammad Bagher Pirouzpanah; Mortaza Raeisi; Nasser Samadi Journal: Asian Pac J Cancer Prev Date: 2017-08-27