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Ziyuglycoside II inhibits the growth of human breast carcinoma MDA-MB-435 cells via cell cycle arrest and induction of apoptosis through the mitochondria dependent pathway.

Zhu X, Wang K, Zhang K, Huang B, Zhang J, Zhang Y, Zhu L, Zhou B, Zhou F - Int J Mol Sci (2013)

Bottom Line: The results showed that ziyuglycoside II could significantly inhibit the growth of MDA-MB-435 cells through blocking cell cycle progression at G0/G1 and S phase as well as via inducing cell apoptosis.Accumulation of reactive oxygen species (ROS) was observed in the progression of cell cycle arrest, which was associated with the increased expression of cell cycle regulating factors, p53 and p21.Subsequent apoptosis induced by ziyuglycoside II was accompanied with the activation of mitochondrial pathway, in particular a decreased mitochondrial membrane potential (MMP) as well as increased Bax/Bcl-2 ratio, cytochrome c release and the activity of caspase-3 and caspase-9.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhuxue0108@gmail.com

ABSTRACT
Ziyuglycoside II is one of the major active compounds of Sanguisorba officinalis L., which has a wide range of clinical applications including hemostasis, antibiosis, anti-inflammation and anti-oxidation. This study investigated the effect of ziyuglycoside II on the growth of human breast carcinoma MDA-MB-435 cells for the first time. The results showed that ziyuglycoside II could significantly inhibit the growth of MDA-MB-435 cells through blocking cell cycle progression at G0/G1 and S phase as well as via inducing cell apoptosis. Accumulation of reactive oxygen species (ROS) was observed in the progression of cell cycle arrest, which was associated with the increased expression of cell cycle regulating factors, p53 and p21. Subsequent apoptosis induced by ziyuglycoside II was accompanied with the activation of mitochondrial pathway, in particular a decreased mitochondrial membrane potential (MMP) as well as increased Bax/Bcl-2 ratio, cytochrome c release and the activity of caspase-3 and caspase-9. In conclusion, our study was the first to report that ziyuglycoside II has inhibitory effect on the growth of MDA-MB-435 cells, which might become a potential therapeutic approach of breast cancer in the future.

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Related in: MedlinePlus

The effect of ziyuglycoside II on expressions of p53 and p21. Cells were incubated with various concentrations of ziyuglycoside II for 24 h and the expressions of p53 and p21 were assessed by Western blot analysis. (Upper panel) Immunobloting of p53 and p21, while β-actin was probed as the protein loading control; (Lower panel): Densitometry analysis of p53 and p21 protein expression. All data were expressed as mean ± SD of three experiments and each experiment included triplicate repeats. * p < 0.05, ** p < 0.01 vs. control.
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f4-ijms-14-18041: The effect of ziyuglycoside II on expressions of p53 and p21. Cells were incubated with various concentrations of ziyuglycoside II for 24 h and the expressions of p53 and p21 were assessed by Western blot analysis. (Upper panel) Immunobloting of p53 and p21, while β-actin was probed as the protein loading control; (Lower panel): Densitometry analysis of p53 and p21 protein expression. All data were expressed as mean ± SD of three experiments and each experiment included triplicate repeats. * p < 0.05, ** p < 0.01 vs. control.

Mentions: To determine the involvement of cell cycle regulating factors in the ziyuglycoside II-induced cell cycle arrest, we evaluated the protein expressions of two key protein factors, p53 and p21, through western blot analysis. Our results revealed that the treatment of ziyuglycoside II on MDA-MB-435 cells resulted in increased expressions of both p53 and p21, which effect was dose-dependent (Figure 4).


Ziyuglycoside II inhibits the growth of human breast carcinoma MDA-MB-435 cells via cell cycle arrest and induction of apoptosis through the mitochondria dependent pathway.

Zhu X, Wang K, Zhang K, Huang B, Zhang J, Zhang Y, Zhu L, Zhou B, Zhou F - Int J Mol Sci (2013)

The effect of ziyuglycoside II on expressions of p53 and p21. Cells were incubated with various concentrations of ziyuglycoside II for 24 h and the expressions of p53 and p21 were assessed by Western blot analysis. (Upper panel) Immunobloting of p53 and p21, while β-actin was probed as the protein loading control; (Lower panel): Densitometry analysis of p53 and p21 protein expression. All data were expressed as mean ± SD of three experiments and each experiment included triplicate repeats. * p < 0.05, ** p < 0.01 vs. control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3794768&req=5

f4-ijms-14-18041: The effect of ziyuglycoside II on expressions of p53 and p21. Cells were incubated with various concentrations of ziyuglycoside II for 24 h and the expressions of p53 and p21 were assessed by Western blot analysis. (Upper panel) Immunobloting of p53 and p21, while β-actin was probed as the protein loading control; (Lower panel): Densitometry analysis of p53 and p21 protein expression. All data were expressed as mean ± SD of three experiments and each experiment included triplicate repeats. * p < 0.05, ** p < 0.01 vs. control.
Mentions: To determine the involvement of cell cycle regulating factors in the ziyuglycoside II-induced cell cycle arrest, we evaluated the protein expressions of two key protein factors, p53 and p21, through western blot analysis. Our results revealed that the treatment of ziyuglycoside II on MDA-MB-435 cells resulted in increased expressions of both p53 and p21, which effect was dose-dependent (Figure 4).

Bottom Line: The results showed that ziyuglycoside II could significantly inhibit the growth of MDA-MB-435 cells through blocking cell cycle progression at G0/G1 and S phase as well as via inducing cell apoptosis.Accumulation of reactive oxygen species (ROS) was observed in the progression of cell cycle arrest, which was associated with the increased expression of cell cycle regulating factors, p53 and p21.Subsequent apoptosis induced by ziyuglycoside II was accompanied with the activation of mitochondrial pathway, in particular a decreased mitochondrial membrane potential (MMP) as well as increased Bax/Bcl-2 ratio, cytochrome c release and the activity of caspase-3 and caspase-9.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhuxue0108@gmail.com

ABSTRACT
Ziyuglycoside II is one of the major active compounds of Sanguisorba officinalis L., which has a wide range of clinical applications including hemostasis, antibiosis, anti-inflammation and anti-oxidation. This study investigated the effect of ziyuglycoside II on the growth of human breast carcinoma MDA-MB-435 cells for the first time. The results showed that ziyuglycoside II could significantly inhibit the growth of MDA-MB-435 cells through blocking cell cycle progression at G0/G1 and S phase as well as via inducing cell apoptosis. Accumulation of reactive oxygen species (ROS) was observed in the progression of cell cycle arrest, which was associated with the increased expression of cell cycle regulating factors, p53 and p21. Subsequent apoptosis induced by ziyuglycoside II was accompanied with the activation of mitochondrial pathway, in particular a decreased mitochondrial membrane potential (MMP) as well as increased Bax/Bcl-2 ratio, cytochrome c release and the activity of caspase-3 and caspase-9. In conclusion, our study was the first to report that ziyuglycoside II has inhibitory effect on the growth of MDA-MB-435 cells, which might become a potential therapeutic approach of breast cancer in the future.

Show MeSH
Related in: MedlinePlus