Encapsulation in PLGA-PEG enhances 9- nitro-camptothecin cytotoxicity to human ovarian carcinoma cell line through apoptosis pathway.
Ovarian cancer is the fifth leading cause of the cancer-related death among women. 9-nitrocamptothecin (9-NC) is a water-insoluble derivative of camptothecin used for the treatment of patients with advanced ovarian cancer. Previous studies showed that the encapsulation of 9-NC in poly (lactic-co-glycolic acid, PLGA) nanoparticles increased the cytotoxic effect of the drug on different cancer cell lines. In the present study, the cytotoxic effects of 9-NC, 9-NC-loaded PLGA and PLGA-polyethylene glycol (PLGA-PEG) nanoparticles with varying degree of PEG (5, 10, and 15%) were evaluated on human ovarian carcinoma cell line. Furthermore, the mode of cell death induced by 9-NC and the optimized 9-NC-loaded PLGA-PEG nanoparticles on A2780 cell line were investigated. 9-NC incorporating nanoparticles were prepared by nanopercipitation method and their physicochemical characteristics were evaluated using standard methods. The results showed that activation of caspase-3 and -9 significantly increased by free 9-NC and PLGA-PEG loaded nanoparticles in A2780 cells. In contrast to the free drug which increased the activation of caspase-8, 9-NC-loaded PLGA-PEG nanoparticles did not alter the activation of caspase-8. Collectively, it appears that apoptosis induced by 9-NC incorporated in PLGA-PEG 5% occurred through the activation of caspase-9 rather than activation of caspase-8 which is the mediator of extrinsic pathway. Moreover, our results confirmed that 9-NC in nanoparticles at the level of gene expression potentiated down-regulation of Bcl-2, up regulation of Bax, and Smac/DIABLO leading to a decrease in mitochondrial membrane potential. Taken together, our results showed that 9-NC incorporated in PLGA-PEG 5% nanoparticles is able to induce apoptosis in A2780 human ovarian carcinoma cells and has the potential for the treatment of ovarian carcinoma.
Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.
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Ahmadi
Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.
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Derakhshandeh
Students research committee, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.
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Jalalizadeh
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.
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Mostafaie
Novel Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.
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Hosseinzadeh
9- Nitrocamptothecin; A2780 ovarian carcinoma cell line; Apoptosis; PLGA-PEG nanoparticles