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PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.

Bishayee K, Khuda-Bukhsh AR, Huh SO - Mol. Cells (2015)

Bottom Line: A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells.NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage.NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea.

ABSTRACT
Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and cell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as p21(WAF), cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the action of the nano-particles on HepG2 cells
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f8-molce-38-6-518: Schematic representation of the action of the nano-particles on HepG2 cells

Mentions: We hypothesize that NQ downregulates HDACs and p21, which may be correlated with cell cycle arrest. The decrease in Cdk1 and pAkt may have resulted in arrest of HepG2 cell proliferation. The flow cytometry analysis demonstrated that NQ arrested the HepG2 cell cycle in the sub-G phase and decreased cell populations in the synthetic and mitotic phases. As most anti-neoplastic drugs in clinical use block the cell cycle in the S or G2/M phases, whereas NQ blocked the cell cycle in the sub-G phase, a combination of NQ with currently used drugs could improve the efficacy of current hepatocarcinoma therapies (Fig. 8). In general, NQ treatment induced ROS and mitochondrial membrane depolarization, and the release of cytochrome c induced apoptosis in HepG2 cells by activating caspase 3. Thus, ROS and p53 shared a combined role.


PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.

Bishayee K, Khuda-Bukhsh AR, Huh SO - Mol. Cells (2015)

Schematic representation of the action of the nano-particles on HepG2 cells
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4469909&req=5

f8-molce-38-6-518: Schematic representation of the action of the nano-particles on HepG2 cells
Mentions: We hypothesize that NQ downregulates HDACs and p21, which may be correlated with cell cycle arrest. The decrease in Cdk1 and pAkt may have resulted in arrest of HepG2 cell proliferation. The flow cytometry analysis demonstrated that NQ arrested the HepG2 cell cycle in the sub-G phase and decreased cell populations in the synthetic and mitotic phases. As most anti-neoplastic drugs in clinical use block the cell cycle in the S or G2/M phases, whereas NQ blocked the cell cycle in the sub-G phase, a combination of NQ with currently used drugs could improve the efficacy of current hepatocarcinoma therapies (Fig. 8). In general, NQ treatment induced ROS and mitochondrial membrane depolarization, and the release of cytochrome c induced apoptosis in HepG2 cells by activating caspase 3. Thus, ROS and p53 shared a combined role.

Bottom Line: A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells.NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage.NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea.

ABSTRACT
Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and cell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as p21(WAF), cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.

No MeSH data available.


Related in: MedlinePlus