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Encapsulation in PLGA-PEG enhances 9- nitro-camptothecin cytotoxicity to human ovarian carcinoma cell line through apoptosis pathway.

Ahmadi F, Derakhshandeh K, Jalalizadeh A, Mostafaie A, Hosseinzadeh L - Res Pharm Sci (2015 Mar-Apr)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cytotoxic effects of 9-NC and 9-NC nanoparticles in A2780 cancer cells. The cells were incubated with different concentrations of 9-NC and 9-NC nanoparticles for 24 h. The cell proliferation inhibition was determined by MTT assay as described under materials and methods. Data are presented as mean ± S.E.M (n=3).
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Figure 2: Cytotoxic effects of 9-NC and 9-NC nanoparticles in A2780 cancer cells. The cells were incubated with different concentrations of 9-NC and 9-NC nanoparticles for 24 h. The cell proliferation inhibition was determined by MTT assay as described under materials and methods. Data are presented as mean ± S.E.M (n=3).

Mentions: The concentration-response curves were generated and the drug sensitivity was expressed as a drug concentration that caused 50% growth inhibition (IC50). As shown in Fig. 2, treatment with 9-NC-loaded nanoparticles shifted the 9-NC concentration-response curve to a lower IC50 values in a dose-dependent manner. The average IC50 values of 9-NC, 9-NC-loaded nanoparticles are shown in the Table 2.


Encapsulation in PLGA-PEG enhances 9- nitro-camptothecin cytotoxicity to human ovarian carcinoma cell line through apoptosis pathway.

Ahmadi F, Derakhshandeh K, Jalalizadeh A, Mostafaie A, Hosseinzadeh L - Res Pharm Sci (2015 Mar-Apr)

Cytotoxic effects of 9-NC and 9-NC nanoparticles in A2780 cancer cells. The cells were incubated with different concentrations of 9-NC and 9-NC nanoparticles for 24 h. The cell proliferation inhibition was determined by MTT assay as described under materials and methods. Data are presented as mean ± S.E.M (n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4584455&req=5

Figure 2: Cytotoxic effects of 9-NC and 9-NC nanoparticles in A2780 cancer cells. The cells were incubated with different concentrations of 9-NC and 9-NC nanoparticles for 24 h. The cell proliferation inhibition was determined by MTT assay as described under materials and methods. Data are presented as mean ± S.E.M (n=3).
Mentions: The concentration-response curves were generated and the drug sensitivity was expressed as a drug concentration that caused 50% growth inhibition (IC50). As shown in Fig. 2, treatment with 9-NC-loaded nanoparticles shifted the 9-NC concentration-response curve to a lower IC50 values in a dose-dependent manner. The average IC50 values of 9-NC, 9-NC-loaded nanoparticles are shown in the Table 2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus