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The Inhibitory Effect of 3 β -Hydroxy-12-oleanen-27-oic Acid on Growth and Motility of Human Hepatoma HepG2 Cells through JNK and Akt Signaling Pathway.

Wang J, Chen X, Zhou Z, Li J, Sun H - Evid Based Complement Alternat Med (2013)

Bottom Line: 3 β -Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes of Astilbe chinensis.PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4.These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

ABSTRACT
3 β -Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes of Astilbe chinensis. In this study, we investigated its effects on growth, apoptosis, cell cycle, motility/invasion, and metatasis in human hepatoma HepG2 cells in vitro and antimetastasis of B16-F10 melanoma in mice in vivo, as well as its molecular mechanisms of action using a high-throughput Cancer Pathway Finder PCR Array. ATA could not only induce tumor cells into apoptosis through the activation of both extrinsic and intrinsic pathways, arrest HepG2 cells in G2/M phase, but also suppress the invasion and metastasis abilities of HepG2 cells and the lung metastasis of B16-F10 melanoma in mice. PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4. These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

No MeSH data available.


Related in: MedlinePlus

Effect of 3β-hydroxy-12-oleanen-27-oic acid (ATA) on the mitochondrial transmembrane potential (Δψm) in HepG2 cells. HepG2 cells were treated with ATA at the concentrations of 0, 5, and 10 μg/mL for 24 and 48 h. (a) Fluorescence changes were visualized under a fluorescence microscope after JC-1 staining. The figures shown were representative of three independent experiments. (b) The staining fluorescence was determined by flow cytometry, and the results were expressed by the ratio of green and red fluorescence. The values are presented as mean ± SD for three independent experiments. Significant differences with 0 μg/mL were designated as ***P < 0.001.
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fig4: Effect of 3β-hydroxy-12-oleanen-27-oic acid (ATA) on the mitochondrial transmembrane potential (Δψm) in HepG2 cells. HepG2 cells were treated with ATA at the concentrations of 0, 5, and 10 μg/mL for 24 and 48 h. (a) Fluorescence changes were visualized under a fluorescence microscope after JC-1 staining. The figures shown were representative of three independent experiments. (b) The staining fluorescence was determined by flow cytometry, and the results were expressed by the ratio of green and red fluorescence. The values are presented as mean ± SD for three independent experiments. Significant differences with 0 μg/mL were designated as ***P < 0.001.

Mentions: The reduction of Δψm plays a marked role in early apoptotic cells. JC-1 is an ideal fluorescent probe to detect the change of Δψm, which exhibit red fluorescence as JC-1 aggregates in mitochondrial matrix under high mitochondrial potential but green fluorescence as monomeric form under low potential. To study the potential effects of ATA on the mitochondrial apoptotic pathway, the change of Δψm in HepG2 cells treated with ATA was measured with JC-1 staining. As shown in Figure 4(a), compared to control cells, the intension of green fluorescence was markedly increased, while that of red fluorescence was highly decreased dose-dependently in ATA-treated HepG2 cells, suggesting that ATA reduced the Δψm in HepG2 cells in dose- and time-dependent manners. Meanwhile, in order to quantitatively analyze the changes of Δψm after ATA treatment, cells were determined using flow cytometry and the relative changed values were presented with the ratio of green to red fluorescence. As shown in Figure 4(b), the ratio of green to red fluorescence in HepG2 cells treated with ATA significantly increased, which was consistent with the observation under fluorescence microscope. These results suggest that ATA could decrease the Δψm without altering plasma membrane permeability in HepG2 cells.


The Inhibitory Effect of 3 β -Hydroxy-12-oleanen-27-oic Acid on Growth and Motility of Human Hepatoma HepG2 Cells through JNK and Akt Signaling Pathway.

Wang J, Chen X, Zhou Z, Li J, Sun H - Evid Based Complement Alternat Med (2013)

Effect of 3β-hydroxy-12-oleanen-27-oic acid (ATA) on the mitochondrial transmembrane potential (Δψm) in HepG2 cells. HepG2 cells were treated with ATA at the concentrations of 0, 5, and 10 μg/mL for 24 and 48 h. (a) Fluorescence changes were visualized under a fluorescence microscope after JC-1 staining. The figures shown were representative of three independent experiments. (b) The staining fluorescence was determined by flow cytometry, and the results were expressed by the ratio of green and red fluorescence. The values are presented as mean ± SD for three independent experiments. Significant differences with 0 μg/mL were designated as ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3860155&req=5

fig4: Effect of 3β-hydroxy-12-oleanen-27-oic acid (ATA) on the mitochondrial transmembrane potential (Δψm) in HepG2 cells. HepG2 cells were treated with ATA at the concentrations of 0, 5, and 10 μg/mL for 24 and 48 h. (a) Fluorescence changes were visualized under a fluorescence microscope after JC-1 staining. The figures shown were representative of three independent experiments. (b) The staining fluorescence was determined by flow cytometry, and the results were expressed by the ratio of green and red fluorescence. The values are presented as mean ± SD for three independent experiments. Significant differences with 0 μg/mL were designated as ***P < 0.001.
Mentions: The reduction of Δψm plays a marked role in early apoptotic cells. JC-1 is an ideal fluorescent probe to detect the change of Δψm, which exhibit red fluorescence as JC-1 aggregates in mitochondrial matrix under high mitochondrial potential but green fluorescence as monomeric form under low potential. To study the potential effects of ATA on the mitochondrial apoptotic pathway, the change of Δψm in HepG2 cells treated with ATA was measured with JC-1 staining. As shown in Figure 4(a), compared to control cells, the intension of green fluorescence was markedly increased, while that of red fluorescence was highly decreased dose-dependently in ATA-treated HepG2 cells, suggesting that ATA reduced the Δψm in HepG2 cells in dose- and time-dependent manners. Meanwhile, in order to quantitatively analyze the changes of Δψm after ATA treatment, cells were determined using flow cytometry and the relative changed values were presented with the ratio of green to red fluorescence. As shown in Figure 4(b), the ratio of green to red fluorescence in HepG2 cells treated with ATA significantly increased, which was consistent with the observation under fluorescence microscope. These results suggest that ATA could decrease the Δψm without altering plasma membrane permeability in HepG2 cells.

Bottom Line: 3 β -Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes of Astilbe chinensis.PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4.These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

ABSTRACT
3 β -Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes of Astilbe chinensis. In this study, we investigated its effects on growth, apoptosis, cell cycle, motility/invasion, and metatasis in human hepatoma HepG2 cells in vitro and antimetastasis of B16-F10 melanoma in mice in vivo, as well as its molecular mechanisms of action using a high-throughput Cancer Pathway Finder PCR Array. ATA could not only induce tumor cells into apoptosis through the activation of both extrinsic and intrinsic pathways, arrest HepG2 cells in G2/M phase, but also suppress the invasion and metastasis abilities of HepG2 cells and the lung metastasis of B16-F10 melanoma in mice. PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4. These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

No MeSH data available.


Related in: MedlinePlus