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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

The pH dependence equilibrium between lacton and carboxylate forms.
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Figure 1: The pH dependence equilibrium between lacton and carboxylate forms.

Mentions: 9-Nitrocamptothecin (9-NC) (Fig. 1) is one of the anticancer drugs that acting against a broad spectrum of cancers (123). Similar to the parent compound camptothecin, the derivative anticancer drug, 9-NC, interferes with the mechanism of action of the nuclear enzyme topoisomerase1 (4). Previous studies have shown that the anti tumor activity of 9-NC is greater than parent drug camptothecin in human tumor xenografted in nude mice (4).


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)

The pH dependence equilibrium between lacton and carboxylate forms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The pH dependence equilibrium between lacton and carboxylate forms.
Mentions: 9-Nitrocamptothecin (9-NC) (Fig. 1) is one of the anticancer drugs that acting against a broad spectrum of cancers (123). Similar to the parent compound camptothecin, the derivative anticancer drug, 9-NC, interferes with the mechanism of action of the nuclear enzyme topoisomerase1 (4). Previous studies have shown that the anti tumor activity of 9-NC is greater than parent drug camptothecin in human tumor xenografted in nude mice (4).

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