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Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

ABSTRACT: Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

SUBMITTER: Ebrahimnezhad Z

PROVIDER: S-EPMC3713872 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

Ebrahimnezhad Zohreh Z Zarghami Nosratollah N Keyhani Manoutchehr M Amirsaadat Soumaye S Akbarzadeh Abolfazl A Rahmati Mohammad M Mohammad Taheri Zohreh Z Nejati-Koshki Kazem K

BioImpacts : BI 20130523 2

Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effec ...[more]

PMID: 23878789

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Project description:?-Sitosterol (?-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate ?-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. ?-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (?-Sit-PLGA and ?-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. ?-Sit-PLGA and ?-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of -13.8 ± 1.61 and -23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of ?-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. ?-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas ?-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that ?-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to ?-Sit-PEG-PLA nanoparticles. ?-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64?53.08 ?g/mL compared to the untreated cells. Taken together, encapsulation of ?-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells.

Dataset Information

Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

Publications

Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

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