Cell cytotoxicity of alpha interferon alone and in combination with nano particles against breast cancer cell line

Abstract

Despite extensive research, most anticancer drugs have nonspecific toxicity. Pharmacological experiments, using dozens of animals for every new compound, most often needed more time for biological characterization than for chemical synthesis. This situation started to change about thirty years ago. Slowly rational approaches developed, like QSAR and molecular modeling. Such cytotoxic drugs have a narrow therapeutic window, which limits their efficacy and results in severe side effects. The use of biological response modifiers and immunotherapy is one of the newer approach to the treatment of cancer and other diseases .Alpha interferon (α-IFN) , the first biologic agent tested ,is now widely available and used to treat a growing number of illnesses. The cytotoxicities of SWNT-IFN , IFN and peg-PLGA -IFN with different concentrations against 4T1after 24 ,48,72hours were evaluated using the MTT assay. The aim of this study was to establish an in vitro model for culturing 4T1 mice breast cancer cell line by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5dipheny tetrazolium bromide] assay.MTT assay was used to assess the viability percent of 4T1 cell culture after 24,48,72 h with different concentration of treatment . the higher toxicity was observed at all concentration of Peg-PLGA –IFN in all time (24,48,72 h) In an attempt to reduce the side effects associated human leukocyte IFN, we investigated physicochemical properties of alpha-interferon subunits with computational study. The structure of protein α-interferon was selected from the protein data bank (PDB code 1RH2). We choose Monte Carlo and on the compute menu and Amber force fields for molecular mechanics calculations. Temperatures of calculation were kept 288-315 K. Moreover, additional parameters were calculated using the QSAR Properties Module of HyperChem 8.4 software. we measured partial derivative of each subunit in constant and variable volume and temperature. we obtained curves and equations of each subunits , at last we administered differential equation of alpha- interferon subunits by using thermodynamic data of energy and QSAR parameters. this survey results will help us find the best sub units for binding to nano-tubes and the best active subunits to cross the cell membrane.