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Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration.

Liu J, Bai J, Jiang G, Li X, Wang J, Wu D, Owusu L, Zhang E, Li W - PLoS ONE (2015)

Bottom Line: Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties.The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway.PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, China.

ABSTRACT
Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management.

No MeSH data available.


Related in: MedlinePlus

PMBPs suppress MMP-9 activity and expression.The cells were treated with PMBPs (0, 5, 10, 25 μg/ml) for 24 h. (A) Activity of MMP-9 in the cell supernatant at various concentrations of PMBPs was examined by gelatin zymography assay. The white bands represent MMP-9 mediated gelatin digestion. (B) The protein expression of MMP-9 in A2780 cells at various concentrations of PMBPs was evaluated by Western blot. Histogram shows mean level of MMP-9 (±SD) from three independent experiments. MMP-9 protein level was expressed relative to loading control, β-Actin, and standardized to the non-treated control group. *P<0.05 and **P<0.01 compared to the control group.
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pone.0142157.g007: PMBPs suppress MMP-9 activity and expression.The cells were treated with PMBPs (0, 5, 10, 25 μg/ml) for 24 h. (A) Activity of MMP-9 in the cell supernatant at various concentrations of PMBPs was examined by gelatin zymography assay. The white bands represent MMP-9 mediated gelatin digestion. (B) The protein expression of MMP-9 in A2780 cells at various concentrations of PMBPs was evaluated by Western blot. Histogram shows mean level of MMP-9 (±SD) from three independent experiments. MMP-9 protein level was expressed relative to loading control, β-Actin, and standardized to the non-treated control group. *P<0.05 and **P<0.01 compared to the control group.

Mentions: Given the effects of PMBPs on ovarian cancer cell migration and invasion, we further investigated the mechanisms of this process. Since MMP-9 plays an important role in cancer invasion, we next detected MMP-9 enzyme activity and expression after PMBPs treatment. MMP-9 activity in conditioned medium was examined by gelatin zymography, and MMP-9 expression was examined by Western blot. PMBPs dose-dependently suppressed MMP-9 activity (Fig 7A) and reduced MMP-9 protein expression level (P<0.05) (Fig 7B). Thus, the inhibitory activity of PMBPs on the invasiveness of ovarian cancer might be, at least partially, due to the suppression of MMP-9 activity.


Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration.

Liu J, Bai J, Jiang G, Li X, Wang J, Wu D, Owusu L, Zhang E, Li W - PLoS ONE (2015)

PMBPs suppress MMP-9 activity and expression.The cells were treated with PMBPs (0, 5, 10, 25 μg/ml) for 24 h. (A) Activity of MMP-9 in the cell supernatant at various concentrations of PMBPs was examined by gelatin zymography assay. The white bands represent MMP-9 mediated gelatin digestion. (B) The protein expression of MMP-9 in A2780 cells at various concentrations of PMBPs was evaluated by Western blot. Histogram shows mean level of MMP-9 (±SD) from three independent experiments. MMP-9 protein level was expressed relative to loading control, β-Actin, and standardized to the non-treated control group. *P<0.05 and **P<0.01 compared to the control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634942&req=5

pone.0142157.g007: PMBPs suppress MMP-9 activity and expression.The cells were treated with PMBPs (0, 5, 10, 25 μg/ml) for 24 h. (A) Activity of MMP-9 in the cell supernatant at various concentrations of PMBPs was examined by gelatin zymography assay. The white bands represent MMP-9 mediated gelatin digestion. (B) The protein expression of MMP-9 in A2780 cells at various concentrations of PMBPs was evaluated by Western blot. Histogram shows mean level of MMP-9 (±SD) from three independent experiments. MMP-9 protein level was expressed relative to loading control, β-Actin, and standardized to the non-treated control group. *P<0.05 and **P<0.01 compared to the control group.
Mentions: Given the effects of PMBPs on ovarian cancer cell migration and invasion, we further investigated the mechanisms of this process. Since MMP-9 plays an important role in cancer invasion, we next detected MMP-9 enzyme activity and expression after PMBPs treatment. MMP-9 activity in conditioned medium was examined by gelatin zymography, and MMP-9 expression was examined by Western blot. PMBPs dose-dependently suppressed MMP-9 activity (Fig 7A) and reduced MMP-9 protein expression level (P<0.05) (Fig 7B). Thus, the inhibitory activity of PMBPs on the invasiveness of ovarian cancer might be, at least partially, due to the suppression of MMP-9 activity.

Bottom Line: Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties.The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway.PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, China.

ABSTRACT
Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management.

No MeSH data available.


Related in: MedlinePlus