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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Nigella sativa,MDR1,Thymoquinone,Drug transporters,Multi drug resistance
- چکیده:
- چکیده انگلیسی: Objective(s): Thymoquinone (TQ) has valuable medical properties like anticancer effects. Development of multidrug resistance (MDR) phenotype is one of the most important factors in failure of cancer chemotherapy. The aim of this study was to evaluate the mode of interaction of TQ and MDR1, a major MDR-related protein in gastric cancer drug resistant EPG85-257RDB cells, and its parental non-resistant EPG85-257 cells.
Materials and Methods: MTT assay was used to assess the effects of TQ and doxorubicin (DOX) on cell viability of tested cell lines and TQ effect on pump performance. HPLC analyses were used to measure the input and output of TQ in EPG85-257RDB cells. Molecular docking studies were used to identify interactions between TQ and MDR1.
Results: TQ inhibited cell viability in a time and concentration-dependent manner. Co-treatment of the cells with TQ and DOX did not significantly affect the amount of cell viability in comparison with DOX treatment alone. The HPLC analyses showed that more than 90% of TQ entered to EPG85-257RDB during 1 hr of treatment with TQ, but it was unable to exit from the cells. Moreover, there was no difference between influx and efflux amount of TQ in cells with inhibited and non-inhibited MDR1 transporters. Molecular docking studies revealed that TQ had a higher inhibitory constant to bind to active site of MDR1 protein as compared to specific inhibitor (verapamil) and substrate (vinblastine) of this transporter.
Conclusion: These results proposed that TQ does not work as an inhibitor or a substrate of MDR1 transporter.- انتشار مقاله: 02-09-1398
- نویسندگان: Vahideh Keyvani,Zeynab Naserifar,Mohammad-Reza Saberi,Seyed Ahmad Mohajeri,Sepideh Arabzadeh,Farajollah Shahriari Ahmadi,Hossein Hosseinzadeh,Seyedeh Mahya Shariat Razavi,Fatemeh Kalalinia
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Nigella sativa,MDR1,Thymoquinone,Drug transporters,Multi drug resistance
- چکیده:
- چکیده انگلیسی: Objective(s): Thymoquinone (TQ) has valuable medical properties like anticancer effects. Development of multidrug resistance (MDR) phenotype is one of the most important factors in failure of cancer chemotherapy. The aim of this study was to evaluate the mode of interaction of TQ and MDR1, a major MDR-related protein in gastric cancer drug resistant EPG85-257RDB cells, and its parental non-resistant EPG85-257 cells.
Materials and Methods: MTT assay was used to assess the effects of TQ and doxorubicin (DOX) on cell viability of tested cell lines and TQ effect on pump performance. HPLC analyses were used to measure the input and output of TQ in EPG85-257RDB cells. Molecular docking studies were used to identify interactions between TQ and MDR1.
Results: TQ inhibited cell viability in a time and concentration-dependent manner. Co-treatment of the cells with TQ and DOX did not significantly affect the amount of cell viability in comparison with DOX treatment alone. The HPLC analyses showed that more than 90% of TQ entered to EPG85-257RDB during 1 hr of treatment with TQ, but it was unable to exit from the cells. Moreover, there was no difference between influx and efflux amount of TQ in cells with inhibited and non-inhibited MDR1 transporters. Molecular docking studies revealed that TQ had a higher inhibitory constant to bind to active site of MDR1 protein as compared to specific inhibitor (verapamil) and substrate (vinblastine) of this transporter.
Conclusion: These results proposed that TQ does not work as an inhibitor or a substrate of MDR1 transporter.- انتشار مقاله: 02-09-1398
- نویسندگان: Vahideh Keyvani,Zeynab Naserifar,Mohammad-Reza Saberi,Seyed Ahmad Mohajeri,Sepideh Arabzadeh,Farajollah Shahriari Ahmadi,Hossein Hosseinzadeh,Seyedeh Mahya Shariat Razavi,Fatemeh Kalalinia
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Doxorubicin,Gastric cancer,Multidrug Resistance,MDR1,Crocin
- چکیده:
- چکیده انگلیسی: Background: Crocin is one of the substantial constituents of saffron extract. It has multiple clinical effects including anti-cancer effects. The development of the multidrug resistance (MDR) phenotype is one of the principal causes of cancer chemotherapy failure. The multidrug resistance protein 1 (MDR1) is one of the MDR-related protein and is often overexpressed in different cancers. In the present study, we aimed to evaluate the influence of crocin on the expression and function of MDR1 protein in EPG85-257 and EPG85-257RDB gastric cancer cell lines. Methods: The cytotoxicity effect of crocin was evaluated by the MTT assay. The impacts of crocin on the expression and function of MDR1 were assessed by Real-time RT-PCR and MTT assay, respectively. Results: The results demonstrated that crocin decreased cell viability in a dose-dependent manner with higher intensity on the EPG85-257 than the EPG85-257RDB cells. Crocin did not make any significant changes in the MDR1 gene expression level in EPG85-257 and EPG85-257RDB cell lines. In contrast, crocin increased doxorubicin cytotoxicity in drug-resistant cells, which might be induced by reduced MDR1 activity. Conclusion: In summary, although crocin did not affect mRNA expression of MDR1, results of MTT assay suggest that it might inhibit the MDR1 function.
- انتشار مقاله: 06-09-1398
- نویسندگان: Seyedeh Mahya Shariat Razavi,Reyhaneh Mahmoudzadeh Vaziri,Gholamreza Karimi,Sepideh Arabzadeh,Vahideh Keyvani,Javad Behravan,Fatemeh Kalalinia
- مشاهده