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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Nanomedicine Journal
- نوع مقاله: Journal Article
- کلمات کلیدی: Gene Therapy,Liposome,siRNA delivery,Nanolipoparticles,PEG-shielded
- چکیده:
- چکیده انگلیسی: Objective(s):
Lipid-based nanoparticles (NLP) are PEGylated carriers composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The presence of PEG in the NLP formulation improves the particle pharmacokinetic behavior. The purpose of this study was to prepare and characterize NLPs containing MDR1 siRNA and evaluate their cytotoxicity and cellular uptake. MDR1 siRNA could be used in multidrug resistance reversal in cancer therapy.
Materials and Methods:
siRNAs were encapsulated into NLPs consisted of mPEG-DSPE/DOTAP/DOPE (10:50:40 molar ratio) by the detergent dialysis method. The particle diameters of NLPs and their surface charge were measured using dynamic light scattering. siRNA encapsulation efficiency was determined by an indirect method via filtration and free siRNA concentration determination. NLPs cytotoxicity was investigated by MTT assay. The ability of NLPs for siRNA delivery checked in two human cell lines (MCF-7/ADR and EPP85-181/RDB) by fluorescence microscopy and compared with oligofectamine.
Results:
NLPs containing MDR1 siRNA were prepared with the stable size of 80-90 nm and the zeta potential near to neutral. The siRNA encapsulation efficacy was more than 80%. These properties are suitable for in vivo siRNA delivery. NLPs cytotoxicity studies demonstrated they were non-toxic at the doses used. NLPs improved siRNA localization in both cell lines.
Conclusion:
NLPs containing MDR1 siRNA can be a good candidate for in vivo siRNA delivery studies.- انتشار مقاله: 06-08-1393
- نویسندگان: Mahnaz Nourbakhsh,Javad Behravan,Hermann Lage,Khalil Abnous,Fatemeh Mosaffa,Ali Badiee,Mahmoud R. Jaafari
- مشاهده
- جایگاه : پژوهشی
- مجله: Nanomedicine Journal
- نوع مقاله: Journal Article
- کلمات کلیدی: Gene Therapy,Liposome,siRNA delivery,Nanolipoparticles,PEG-shielded
- چکیده:
- چکیده انگلیسی: Objective(s):
Lipid-based nanoparticles (NLP) are PEGylated carriers composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The presence of PEG in the NLP formulation improves the particle pharmacokinetic behavior. The purpose of this study was to prepare and characterize NLPs containing MDR1 siRNA and evaluate their cytotoxicity and cellular uptake. MDR1 siRNA could be used in multidrug resistance reversal in cancer therapy.
Materials and Methods:
siRNAs were encapsulated into NLPs consisted of mPEG-DSPE/DOTAP/DOPE (10:50:40 molar ratio) by the detergent dialysis method. The particle diameters of NLPs and their surface charge were measured using dynamic light scattering. siRNA encapsulation efficiency was determined by an indirect method via filtration and free siRNA concentration determination. NLPs cytotoxicity was investigated by MTT assay. The ability of NLPs for siRNA delivery checked in two human cell lines (MCF-7/ADR and EPP85-181/RDB) by fluorescence microscopy and compared with oligofectamine.
Results:
NLPs containing MDR1 siRNA were prepared with the stable size of 80-90 nm and the zeta potential near to neutral. The siRNA encapsulation efficacy was more than 80%. These properties are suitable for in vivo siRNA delivery. NLPs cytotoxicity studies demonstrated they were non-toxic at the doses used. NLPs improved siRNA localization in both cell lines.
Conclusion:
NLPs containing MDR1 siRNA can be a good candidate for in vivo siRNA delivery studies.- انتشار مقاله: 06-08-1393
- نویسندگان: Mahnaz Nourbakhsh,Javad Behravan,Hermann Lage,Khalil Abnous,Fatemeh Mosaffa,Ali Badiee,Mahmoud R. Jaafari
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: 3,Anticancer activity Molecular docking Oxazinonaphthalene,one Resistant cancer cells Tubulin polymerization
- چکیده:
- چکیده انگلیسی: Objective(s): In the present study, a new series of oxazinonaphthalene-3-one analogs was designed and synthesized as novel tubulin inhibitors.
Materials and Methods: The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma), A2780/RCIS (cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), and MCF-7/MX (mitoxantrone resistant human breast cancer cells), those compounds which demonstrated the most antiproliferative activity in the MTT test were selected to investigate their tubulin inhibition activity and their effects on cell cycle arrest (at the G2/M phase). Moreover, molecular docking studies of the selected compounds in the catalytic site of tubulin (PDB ID: 4O2B) were carried out to describe the results of biological experiments.
Results: Most of our compounds exhibited significant to moderate cytotoxic activity against four human cancer cell lines. Among them, Compounds 4d, 5c, and 5g, possessing trimethoxy phenyl, showed the most antiproliferative activity with IC50 values ranging from 4.47 to 52.8 μM.
Conclusion: The flow cytometric analysis of A2780 cancer cell line treated with compounds 4d, 5c, and 5g showed that these compounds induced cell cycle arrest at the G2/M phase. Compound 5g, the most antiproliferative compound, inhibited tubulin polymerization in a dose-dependent manner. Molecular docking studies of 5g into the colchicine-binding site of tubulin displayed a possible mode of interaction between this compound and tubulin.- انتشار مقاله: 11-03-1398
- نویسندگان: Salimeh Mirzaei,Maqsudjon Qayumov,Fahimeh Ganji,Javad Behravan,Razieh Ghodsi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Multidrug Resistance,TNF-α,mitoxantrone,14-3-3 γ,MCF-7/MX cells
- چکیده:
- چکیده انگلیسی: Objective(s): Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α.
Materials and Methods: Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results.
Results: Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α.
Conclusion: Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.- انتشار مقاله: 11-02-1398
- نویسندگان: Saeed Norouzi,Rezvan Yazdian,Morteza Ghanaian,Khalil Abnous,Javad Behravan,Fatemeh Mosaffa
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Crocetin,A2780,A2780-RCIS,MRP,Ovarian cancer cell line
- چکیده:
- چکیده انگلیسی: Objective(s): Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP1 and MRP2 activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).
Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP1 and MRP2 expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay.
Results: Crocetin decreased cell proliferation in the A2780 (IC50: 183±7 µM) and A2780-RCIS (IC50: 316±9 µM). Crocetin decreased the expression level of MRP1 (22±2 %) and MRP2 (48±8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44±1 %) and A2780-RCIS (88±10 %) and indirectly in A2780 (32±2 %) and A2780-RCIS (48±15 %) respectively.
Conclusion: Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.- انتشار مقاله: 08-11-1396
- نویسندگان: Navid Neyshaburinezhad,Maryam Hashemi,Mohammad Ramezani,Sepideh Arabzadeh,Javad Behravan,Fatemeh Kalalinia
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: 3,Anticancer activity Molecular docking Oxazinonaphthalene,one Resistant cancer cells Tubulin polymerization
- چکیده:
- چکیده انگلیسی: Objective(s): In the present study, a new series of oxazinonaphthalene-3-one analogs was designed and synthesized as novel tubulin inhibitors.
Materials and Methods: The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma), A2780/RCIS (cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), and MCF-7/MX (mitoxantrone resistant human breast cancer cells), those compounds which demonstrated the most antiproliferative activity in the MTT test were selected to investigate their tubulin inhibition activity and their effects on cell cycle arrest (at the G2/M phase). Moreover, molecular docking studies of the selected compounds in the catalytic site of tubulin (PDB ID: 4O2B) were carried out to describe the results of biological experiments.
Results: Most of our compounds exhibited significant to moderate cytotoxic activity against four human cancer cell lines. Among them, Compounds 4d, 5c, and 5g, possessing trimethoxy phenyl, showed the most antiproliferative activity with IC50 values ranging from 4.47 to 52.8 μM.
Conclusion: The flow cytometric analysis of A2780 cancer cell line treated with compounds 4d, 5c, and 5g showed that these compounds induced cell cycle arrest at the G2/M phase. Compound 5g, the most antiproliferative compound, inhibited tubulin polymerization in a dose-dependent manner. Molecular docking studies of 5g into the colchicine-binding site of tubulin displayed a possible mode of interaction between this compound and tubulin.- انتشار مقاله: 11-03-1398
- نویسندگان: Salimeh Mirzaei,Maqsudjon Qayumov,Fahimeh Ganji,Javad Behravan,Razieh Ghodsi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Multidrug Resistance,TNF-α,mitoxantrone,14-3-3 γ,MCF-7/MX cells
- چکیده:
- چکیده انگلیسی: Objective(s): Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α.
Materials and Methods: Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results.
Results: Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α.
Conclusion: Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.- انتشار مقاله: 11-02-1398
- نویسندگان: Saeed Norouzi,Rezvan Yazdian,Morteza Ghanaian,Khalil Abnous,Javad Behravan,Fatemeh Mosaffa
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Crocetin,A2780,A2780-RCIS,MRP,Ovarian cancer cell line
- چکیده:
- چکیده انگلیسی: Objective(s): Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP1 and MRP2 activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).
Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP1 and MRP2 expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay.
Results: Crocetin decreased cell proliferation in the A2780 (IC50: 183±7 µM) and A2780-RCIS (IC50: 316±9 µM). Crocetin decreased the expression level of MRP1 (22±2 %) and MRP2 (48±8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44±1 %) and A2780-RCIS (88±10 %) and indirectly in A2780 (32±2 %) and A2780-RCIS (48±15 %) respectively.
Conclusion: Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.- انتشار مقاله: 08-11-1396
- نویسندگان: Navid Neyshaburinezhad,Maryam Hashemi,Mohammad Ramezani,Sepideh Arabzadeh,Javad Behravan,Fatemeh Kalalinia
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Multidrug Resistance,Gene Therapy,Liposome,siRNA delivery,Tumor targeting
- چکیده:
- چکیده انگلیسی: Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA-mediated P-gp downregulation. Materials and Methods: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamineTM (OFA) in vitro and in vivo. Results: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.
- انتشار مقاله: 13-02-1394
- نویسندگان: Mahnaz Nourbakhsh,Mahmoud Reza Jaafari,Hermann Lage,Khalil Abnous,Fatemeh Mosaffa,Ali Badiee,Javad Behravan
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Apoptosis,Doxorubicin,Curcumin,H9C2 cells
- چکیده:
- چکیده انگلیسی: Objective(s) Doxorubicin (DOX), a widely used chemotherapeutic agent can give rise to serve cardiotoxicity by inducing apoptosis. Curcumin, the active compound of the rhizome of Curcuma longa L. has anti-inflammatory, antioxidant and anti-proliferative activities. Curcumin has been identified to increase cytotoxicity in several cancer cell lines in combination with DOX, but there is no study about its effect and DOX on normal cardiac cells. Therefore, in the present study, we evaluated the effect of curcumin on apoptosis induced by DOX in H9c2 rat heart-derived cells. Materials and Methods Cell viability was determined by MTT assay. Also, activation of caspase-3 was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the expression of c-IAP1. Detection of intracellular DOX accumulation was performed by flow cytometry. Results No toxicity observed when the cells exposed for 1 hr to different concentrations of curcumin, but pretreatment of cells with curcumin increased cytotoxicity of DOX in a dose dependent manner. Analysis of caspase-3 activation showed that curcumin pretreatment increased caspase-3 activation. RT-PCR analysis clearly showed that curcumin significantly decreased mRNA gene expression of c-IAP1 compared to cells treated with DOX alone. Pretreatment of H9c2 cells with DOX and curcumin had no effect on the intracellular accumulation of DOX. Conclusion Our observations indicated that subtoxic concentrations of curcumin sensitize H9c2 cells to DOX-induce apoptosis. These results suggest that the use of curcumin in combination with DOX in malignancy must be reevaluated.
- انتشار مقاله: 29-06-1394
- نویسندگان: Leila Hosseinzadeh,Javad Behravan,Fatemeh Mosaffa,Gholamreza Bahrami,Ahmad Reza Bahrami,Gholamreza Karimi
- مشاهده