Limits...
A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells.

Suk FM, Lien GS, Huang WJ, Chen CN, Lu SY, Yang YC, Yan MD, Liang YC - Evid Based Complement Alternat Med (2013)

Bottom Line: First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners.Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells.These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.

ABSTRACT
Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002) is a Taiwanese propolin G (PPG) derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

No MeSH data available.


Related in: MedlinePlus

The propolis derivative, GS-002, decreased viable cell numbers in human hepatoma cells. (a) Hep3B and (b) HepG2 cells were treated with various concentrations of GS-002 for the indicated time periods, and then viable cell numbers were determined with a crystal violet dye. Values are presented as the mean ± SE of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3814109&req=5

fig2: The propolis derivative, GS-002, decreased viable cell numbers in human hepatoma cells. (a) Hep3B and (b) HepG2 cells were treated with various concentrations of GS-002 for the indicated time periods, and then viable cell numbers were determined with a crystal violet dye. Values are presented as the mean ± SE of three independent experiments.

Mentions: We examined the antitumor effect of GS-002 in human hepatoma cell lines and found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners (Figure 2). In the human hepatoma Hep3B and HepG2 cell lines, GS-002 significantly induced cell death in dose- and time-dependent manners and, respectively, showed 88% and 84% reductions in cell viability with 20 μg/mL of GS-002 at 24 h of treatment.


A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells.

Suk FM, Lien GS, Huang WJ, Chen CN, Lu SY, Yang YC, Yan MD, Liang YC - Evid Based Complement Alternat Med (2013)

The propolis derivative, GS-002, decreased viable cell numbers in human hepatoma cells. (a) Hep3B and (b) HepG2 cells were treated with various concentrations of GS-002 for the indicated time periods, and then viable cell numbers were determined with a crystal violet dye. Values are presented as the mean ± SE of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814109&req=5

fig2: The propolis derivative, GS-002, decreased viable cell numbers in human hepatoma cells. (a) Hep3B and (b) HepG2 cells were treated with various concentrations of GS-002 for the indicated time periods, and then viable cell numbers were determined with a crystal violet dye. Values are presented as the mean ± SE of three independent experiments.
Mentions: We examined the antitumor effect of GS-002 in human hepatoma cell lines and found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners (Figure 2). In the human hepatoma Hep3B and HepG2 cell lines, GS-002 significantly induced cell death in dose- and time-dependent manners and, respectively, showed 88% and 84% reductions in cell viability with 20 μg/mL of GS-002 at 24 h of treatment.

Bottom Line: First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners.Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells.These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.

ABSTRACT
Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002) is a Taiwanese propolin G (PPG) derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

No MeSH data available.


Related in: MedlinePlus