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Induction of Cell Cycle Arrest and Apoptosis by Physcion, an Anthraquinone Isolated From Rhubarb (Rhizomes of Rheum tanguticum), in MDA-MB-231 Human Breast Cancer Cells.

Hong JY, Chung HJ, Bae SY, Trung TN, Bae K, Lee SK - J Cancer Prev (2014)

Bottom Line: Flow cytometric analysis indicated that physcion markedly induced the accumulation of cells in the G0/G1 phase and the increase of cell population in the sub-G1 phase.The G0/G1 cell cycle arrest by physcion was associated with the down-regulation of Cyclin D1, Cyclin A, CDK4, CDK2, c-Myc and phosphorylated Rb protein expressions.The increase of sub-G1 peak by physcion was closely correlated with the induction of apoptosis, which was confirmed by the induction of cleaved poly-(adenosine diphosphate ribose) polymerase, activation of Caspases, and suppression of Bid and Bcl-2 expression.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Seoul National University, Seoul, Korea.

ABSTRACT

Background: Physcion is an anthraquinone from rhubarb (rhizomes of Rheum tanguticum) and has been reported to have anti-inflammatory, hepatoprotective, antifungal, and anti-cancer activities. However, the growth inhibitory activity against human cancer cells and the underlying molecular mechanisms have been poorly determined. This study was designed to investigate the anti-proliferative activity of physcion by induction of cell cycle arrest and apoptosis in human MDA-MB-231 triple negative breast cancer cell line.

Methods: MDA-MB-231 cells were treated with physcion, and the anti-proliferative activity was evaluated by the sulforhodamine B assay. The mechanisms of action for the growth inhibitory activity of physcion were evaluated by flow cytometry for cell cycle distribution, and by Western blot for the assessment of potential target proteins.

Results: Physcion showed a significant anti-proliferative activity against MDA-MB-231 human breast cancer cells. Flow cytometric analysis indicated that physcion markedly induced the accumulation of cells in the G0/G1 phase and the increase of cell population in the sub-G1 phase. The G0/G1 cell cycle arrest by physcion was associated with the down-regulation of Cyclin D1, Cyclin A, CDK4, CDK2, c-Myc and phosphorylated Rb protein expressions. The increase of sub-G1 peak by physcion was closely correlated with the induction of apoptosis, which was confirmed by the induction of cleaved poly-(adenosine diphosphate ribose) polymerase, activation of Caspases, and suppression of Bid and Bcl-2 expression.

Conclusions: The induction of G0/G1 cell cycle arrest and apoptosis might be one of the plausible mechanisms of actions for the anti-proliferative activity of physcion in human breast cancer cells.

No MeSH data available.


Related in: MedlinePlus

Morphological changes mediated by physcion in MDA-MB-231 cells. Cells were treated with various concentrations of physcion for 24 hours. Cells were photographed by inverted microscopy (×100).
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f3-jcp-19-273: Morphological changes mediated by physcion in MDA-MB-231 cells. Cells were treated with various concentrations of physcion for 24 hours. Cells were photographed by inverted microscopy (×100).

Mentions: The anti-proliferative effect of physcion (Fig. 1) was determined in MDA-MB-231 human breast cancer cells by a colorimetric SRB protein dye staining method. As a result, the proliferation of MDA-MB-231 cells exposed to physcion was inhibited in a dose-dependent manner, with an IC50 value 45.4 μM at 72 hours incubation (Fig. 2). In addition, morphological changes were observed using a phase-contrast microscope. As shown in Figure 3, the cells treated with various concentrations (35, 70, and 140 μM) of physcion for 24 hours exhibited distinct cell shrinkage and rounded shapes in a concentration-dependent manner compared to control cells.


Induction of Cell Cycle Arrest and Apoptosis by Physcion, an Anthraquinone Isolated From Rhubarb (Rhizomes of Rheum tanguticum), in MDA-MB-231 Human Breast Cancer Cells.

Hong JY, Chung HJ, Bae SY, Trung TN, Bae K, Lee SK - J Cancer Prev (2014)

Morphological changes mediated by physcion in MDA-MB-231 cells. Cells were treated with various concentrations of physcion for 24 hours. Cells were photographed by inverted microscopy (×100).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4285958&req=5

f3-jcp-19-273: Morphological changes mediated by physcion in MDA-MB-231 cells. Cells were treated with various concentrations of physcion for 24 hours. Cells were photographed by inverted microscopy (×100).
Mentions: The anti-proliferative effect of physcion (Fig. 1) was determined in MDA-MB-231 human breast cancer cells by a colorimetric SRB protein dye staining method. As a result, the proliferation of MDA-MB-231 cells exposed to physcion was inhibited in a dose-dependent manner, with an IC50 value 45.4 μM at 72 hours incubation (Fig. 2). In addition, morphological changes were observed using a phase-contrast microscope. As shown in Figure 3, the cells treated with various concentrations (35, 70, and 140 μM) of physcion for 24 hours exhibited distinct cell shrinkage and rounded shapes in a concentration-dependent manner compared to control cells.

Bottom Line: Flow cytometric analysis indicated that physcion markedly induced the accumulation of cells in the G0/G1 phase and the increase of cell population in the sub-G1 phase.The G0/G1 cell cycle arrest by physcion was associated with the down-regulation of Cyclin D1, Cyclin A, CDK4, CDK2, c-Myc and phosphorylated Rb protein expressions.The increase of sub-G1 peak by physcion was closely correlated with the induction of apoptosis, which was confirmed by the induction of cleaved poly-(adenosine diphosphate ribose) polymerase, activation of Caspases, and suppression of Bid and Bcl-2 expression.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Seoul National University, Seoul, Korea.

ABSTRACT

Background: Physcion is an anthraquinone from rhubarb (rhizomes of Rheum tanguticum) and has been reported to have anti-inflammatory, hepatoprotective, antifungal, and anti-cancer activities. However, the growth inhibitory activity against human cancer cells and the underlying molecular mechanisms have been poorly determined. This study was designed to investigate the anti-proliferative activity of physcion by induction of cell cycle arrest and apoptosis in human MDA-MB-231 triple negative breast cancer cell line.

Methods: MDA-MB-231 cells were treated with physcion, and the anti-proliferative activity was evaluated by the sulforhodamine B assay. The mechanisms of action for the growth inhibitory activity of physcion were evaluated by flow cytometry for cell cycle distribution, and by Western blot for the assessment of potential target proteins.

Results: Physcion showed a significant anti-proliferative activity against MDA-MB-231 human breast cancer cells. Flow cytometric analysis indicated that physcion markedly induced the accumulation of cells in the G0/G1 phase and the increase of cell population in the sub-G1 phase. The G0/G1 cell cycle arrest by physcion was associated with the down-regulation of Cyclin D1, Cyclin A, CDK4, CDK2, c-Myc and phosphorylated Rb protein expressions. The increase of sub-G1 peak by physcion was closely correlated with the induction of apoptosis, which was confirmed by the induction of cleaved poly-(adenosine diphosphate ribose) polymerase, activation of Caspases, and suppression of Bid and Bcl-2 expression.

Conclusions: The induction of G0/G1 cell cycle arrest and apoptosis might be one of the plausible mechanisms of actions for the anti-proliferative activity of physcion in human breast cancer cells.

No MeSH data available.


Related in: MedlinePlus