Synthesis and Characterization of Polymeric Conjugated Sirolimus on MCF-7(Estrogen Positive) and MDA MB 231(Estrogen Negative) Breast Cancer Cell Lines
نویسندگان
چکیده
Sirolimus (SR) is used as an immunosuppressant drug to prevent organ rejection in kidney transplants. It is chemically a macrolide and isolated from the bacterium Streptomyces hygroscopicus in a soil sample. Of recent, it has potent antiproliferative properties and useful in the treatment of certain types of cancer. In our objective of the study, SR is chemically conjugated with Methoxy-polyethylene glycolic acid (mPEG COOH) and Poly(lactic-co glycolic acid)[PLGA]. Two polymeric SR conjugates (mPEG-SR and PLGA-SR) were characterized by UV-spectra, infrared (IR) spectra, 1 H NMR spectra, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and HPLC analyses. It was found to be structurally correlated among the chemical structures of SR, mPEG COOH-SR conjugate, PLGA-SR conjugate, PLGA and m-PEG COOH polymers. The MTT assay of mPEG-SR, PLGA conjugates were carried out on specific MCF-7(Estrogen positive) and MDA MB231 (Estrogen negative) breast cancer cell lines using tamoxifen as control. All results were showing the positive effects of mPEG-SR with IC50 values of 15 μg/ml and 1.5 μg/ml more active than tamoxifen with IC50 values of 28 μg/ml and 4.9 μg/ml on MDAMB 231(estrogen negative) and MCF-7(estrogen positive) breast cancer cell lines in vitro, respectively. Whereas PLGA-SR conjugate was shown high activity on MCF-7(estrogen positive) with IC50 value of 1.2 μg/ml and less activity on MDA MB 231(estrogen negative) with IC50 value of more than 100 μg/ml. Both conjugates have not shown any cytotoxicity activity on 3T3 fibroblast normal cell lines. These results indicate that both conjugates may provide highly potent cytotoxicity activity against specific breast cancer types than SR alone. In conclusion, polymeric conjugation is a useful approach in drug delivery systems. These conjugates are basic precursors to formulate into a novel drug delivery system for better release and with increased good bioavailability with fewer side effects.
منابع مشابه
ADENOSINE DEAMINASE ACTIVITY IN ESTROGEN RECEPTOR POSITIVE AND NEGATIVE HUMAN BREAST CANCER CELL LINES
ABSTRACT Background: The aims of this study were to assay the activity of adenosine deaminase (ADA) in estrogen receptor positive (MCF-7) and negative (MDA-MB468) breast cancer cell lines. Methods: MDA-MB468 and MCF-7 breast cancer cell lines were cultured in complete medium, striped serum with and without 0.0 1~-LM diethylstilbestrol (DES), complete medium in the presence and absence of 111M ...
متن کاملTranscriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB 231 and MCF-7 Breast Cancer Cell Lines
Background: The organochlorine DDT has estrogenic activity but the mechanism underlying the estrogenic activity of this pesticide remains unclear. In the present investigation here, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p’-DDT [1.1.1.-trichloro-2-(o-chlorophenyl)-2-p-chloriphenyl ethane] and its metabolite p,p'-DDE (2-2-bis(4/chlorophenyl)-1-1-di...
متن کاملMetronidazole affects breast cancer cell lines.
PURPOSE The aim of our study was to evaluate the impact of metronidazole (MTZ) on cytotoxicity and DNA synthesis in MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative) breast cancer cell lines. MATERIAL/METHODS Toxicity of MTZ was determined by MTT test. MCF-7 and MDA-MB-231 cells were incubated with metronidazole used in different concentrations for 24, 48 and 72 h...
متن کاملCell Kinetic Study of Tamoxifen Treated MCF-7 and MDA-MB 468 Breast Cancer Cell Lines
Apoptosis could be a major mechanism of antitumor effect of tamoxifen. Therefore this study is designed to characterize the kinetic behavior of tamoxifen-induced apoptosis in the estrogen receptor positive (ER+) and negative (ER-) cell lines, MCF-7 and MDA-MB-468. Frequency of cell death was examined by trypan blue and acridine orange staining. Annexin V-Fluorescein/PI was used in flow cytometr...
متن کاملTHE EFFECT OF QUINACRINE ON THE EXPRESSION OF WNT3A GENE IN MDA-MB 231 AND MCF7 BREAST CANCER CELL LINES
Background & Aims: Triple-negative breast cancer cells refer to any breast cancer that does not express the genes for the estrogen, progesterone, and HER2 receptors. The Wnt signaling pathway is important in the development and progression of various types of cancers. Quinacrine, a derivative of 9-aminoacridine, has been shown to inhibit the growth of several types of cancer cells. In this stud...
متن کامل