The molecular mechanism of gypenosides-induced G1 growth arrest of rat hepatic stellate cells

Chen, Ming-Ho; Chen, Shu-Hsin; Wang, Qwa-Fun; Chen, Jung-Chou; Chang, Deching; Hsu, Shih-Lan; Chen, Ching‐Hsein; Sheue, Chiou‐Rong; Liu, Yiwen

doi:10.1016/j.jep.2008.02.009

Cited by 27 publications

(16 citation statements)

References 23 publications

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“…CD-1, which can be rarely detected in the normal HSCs and non-proliferative senescent HSCs, is overexpressed in culture-activated HSCs and intra-hepatic HSCs after DMN(dimethylnitrosamine) injury [20,21]. Recent studies have partially attributed the proliferation of activated HSCs to the over-expression of CD-1 [20,22]. Furthermore, Using bioinformatics tools, we found that miR-16 was the only miRNA targeting CD-1 with 8 complementary nucleotides.…”

Section: Discussionmentioning

confidence: 84%

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

et al. 2009

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In our previous studies, we identified miR-16 as being downregulated during activation of hepatic stellate cells (HSCs) by microarray hybridization. However, the roles and related mechanisms of miR-16 in HSCs are not understood. In this study, The miRNA RNAi technique was used to analyze the effects of miR-16 on biological properties of HSCs in vitro. The lentiviral vector encoding miR-16 was constructed and transfected. Furthermore, the expression level of miR-16 was measured by real-time PCR. Cellular growth and proliferation capacity were assayed using the cell counting kit-8 (CCK-8). The apoptosis rate and cell-cycle distribution were measured by flow cytometry. Cell morphological characteristics were identified by phase-contrast microscopy, fluorescence microscopy and electron microscopy. The underlying mechanisms related to the changes in biological properties were assessed. The identity of the recombinant plasmid was confirmed by restriction endonuclease analysis and DNA sequencing. Virus titer was 10(8) > ifu/m. Restoring the intracellular miRNAs by miR-16 administration greatly reduced the expression levels of cyclin D1 (CD1). Cell-cycle arrest and typical features of apoptosis were detected in activated HSCs treated with pLV-miR-16. Our results indicate that transduction of miR-16 offers a feasible approach to significantly inhibit HSC proliferation and increase the apoptosis index. Thus, targeted transfer of miR-16 into HSC may be useful for the treatment of hepatic fibrosis.

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Section: Discussionmentioning

confidence: 84%

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

et al. 2009

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“…Chen et al . [67] demonstrate that Gypenosides inhibits PDGF-induced HSCs proliferation through inhibiting the signalling pathway of PDGF-Akt-p70 S6K and down-regulating cyclin D1 and D3 expression. Another study shows that ganoderic acids and ganoderenic acids in Ganoderma lucidum ( Lingzhi ) extract significantly inhibit the proliferation of HSCs by attenuating the blockade of PDGFβR phosphorylation [66].…”

Section: Action Mechanisms Of Chinese Medicines In Treating Liver Fibmentioning

confidence: 99%

Chinese medicines as a resource for liver fibrosis treatment

et al. 2009

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Liver fibrosis is a condition of abnormal proliferation of connective tissue due to various types of chronic liver injury often caused by viral infection and chemicals. Effective therapies against liver fibrosis are still limited. In this review, we focus on research on Chinese medicines against liver fibrosis in three categories, namely pure compounds, composite formulae and combination treatment using single compounds with composite formulae or conventional medicines. Action mechanisms of the anti-fibrosis Chinese medicines, clinical application, herbal adverse events and quality control are also reviewed. Evidence indicates that some Chinese medicines are clinically effective on liver fibrosis. Strict quality control such as research to identify and monitor the manufacturing of Chinese medicines enables reliable pharmacological, clinical and in-depth mechanism studies. Further experiments and clinical trials should be carried out on the platforms that conform to international standards.

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“…11 In human lung A549 cancer cells, Gyp exerted its anticancer properties by inducing G0/G1 arrest and apoptosis via activation of caspase-3. 17 Further, Gyp inhibited invasion and migration of human tongue cancer cells by downregulating NF-kappaB and matrix metalloproteinase-9. 18 Subsequent study showed that an increase in intracellular Ca …”

Section: Introductionmentioning

confidence: 97%

Gypenosides Induce Apoptosis by Ca²⁺ Overload Mediated by Endoplasmic-Reticulum and Store-Operated Ca²⁺ Channels in Human Hepatoma Cells

Sun

Li²,

Liu³

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Gypenosides (Gyps) are triterpenoid saponins contained in an extract from Gynostemma pentaphyllum Makino and reported to induce apoptosis in human hepatoma cells through Ca 2 + -implicated endoplasmic reticulum (ER) stress and mitochondria-dependent pathways. The mechanism underlying the Gyp-increased intracellular Ca 2 + channel (SOC) inhibitor 2-aminoethoxydiphenyl borate (2-APB), and ER Ca 2 + -release-antagonist 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8). The strongest inhibitory effect was observed with TMB-8. EGTA, 2-APB, and TMB-8 also protected against Gyp-induced apoptosis in HepG2 cells. The combination of 2-APB and TMB-8 almost completely abolished the Gyp-induced Ca 2 + response and apoptosis. In contrast, the sarco/endoplasmic-reticulum-Ca 2 + -ATPase (SERCA) inhibitor thapsigargin slightly elevated Gyp-induced [Ca 2 + ] i increase and apoptosis in HepG2 cells. Exposure to 300 lg/mL Gyp for 24 hours upregulated protein levels of inositol 1,4,5-trisphosphate receptor and SOC and downregulated that of SERCA for at least 72 hours. Thus, Gyp-induced increase in [Ca 2 + ] i level and consequent apoptosis in HepG2 cells may be mainly due to enhanced Ca 2 + release from ER stores and increased store-operated Ca 2 + entry.

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The molecular mechanism of gypenosides-induced G1 growth arrest of rat hepatic stellate cells

Cited by 27 publications

References 23 publications

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

Chinese medicines as a resource for liver fibrosis treatment

Gypenosides Induce Apoptosis by Ca²⁺ Overload Mediated by Endoplasmic-Reticulum and Store-Operated Ca²⁺ Channels in Human Hepatoma Cells

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The molecular mechanism of gypenosides-induced G1 growth arrest of rat hepatic stellate cells

Cited by 27 publications

References 23 publications

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

Chinese medicines as a resource for liver fibrosis treatment

Gypenosides Induce Apoptosis by Ca2+ Overload Mediated by Endoplasmic-Reticulum and Store-Operated Ca2+ Channels in Human Hepatoma Cells

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Gypenosides Induce Apoptosis by Ca²⁺ Overload Mediated by Endoplasmic-Reticulum and Store-Operated Ca²⁺ Channels in Human Hepatoma Cells