Caudatin induces cell cycle arrest and caspase-dependent apoptosis in HepG2 cell

Fei, Hong Rong; Chen, Hong Lei; Tu, Xiao; Chen, Geng; Wang, Feng Ze

doi:10.1007/s11033-011-0721-6

Cited by 29 publications

(13 citation statements)

References 23 publications

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“…Nowadays, the use of apoptosis-inducing agents from herbal prescriptions has gained a great deal of interest for the treatment of cancer. These plant extracts have been explored for discovering potential natural therapeutic compounds due to their excellent pharmacological activities and low side effects [3].…”

Section: Introductionmentioning

confidence: 99%

Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells

et al. 2015

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Ethylacetate extract of Tetrastigma hemsleyanum (EET) has a potent antitumor activity in vitro and in vivo. However, the molecular mechanism underlying EET-induced apoptosis remains elusive. As part of our continuing studies, we investigated the apoptosis mechanism of HepG2 cells exposed to different concentrations of EET in vitro. Confocal laser scanning was used to detect the apoptotic morphological changes. Flow cytometer and inverted fluorescence microscope were used to detect the mitochondrial membrane potential and cytosolic Ca(2+) level. Western blotting analysis was used to evaluate the expression of the apoptosis-related proteins. Annexin V/PI staining was used to investigate cell apoptosis. Spectrophotometry was used to detect the activity of caspase family. The results showed that distinct apoptotic morphological changes occurred in HepG2 cells treated by EET. EET caused collapse of mitochondrial membrane potential, elevation of cytosolic Ca(2+) level, and evoked release of cytochrome c from mitochondria in a concentration-dependent manner. The apoptosis was accompanied by a significant activation of caspase-3, caspase-9, and the cleavage of poly (ADP-ribose) polymerase, but there was no significant change in either the activity or the expression level of caspase-8. Furthermore, EET-induced apoptosis could be inhibited by caspase-9 inhibitor Z-LEHD-FMK but not by caspase-8 inhibitor Z-IETD-FMK. Taken together, these overall results demonstrated that EET-induced apoptosis of HepG2 cells was mediated by the mitochondrial caspase-dependent intrinsic pathway rather than the death receptor/caspase-8-mediated signaling route.

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Section: Introductionmentioning

confidence: 99%

Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells

et al. 2015

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“…Caudatin, a C-21 steroidal glycoside, is mainly isolated from the root of Cynanchum bungei Decne in China. Recent studies demonstrated that caudatin induced the apoptosis of HepG2 cells or the SMMC772 cell line (6,7). Wang et al (8) found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication.…”

Section: Introductionmentioning

confidence: 99%

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

Zhang

Liu

et al. 2013

Oncology Reports

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Abstract. Caudatin has been reported to trigger apoptosis in several types of cancer cell lines. In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of β-catenin in human gastric carcinoma cell lines. Here, we showed that caudatin treatment resulted in a dose-and time-dependent inhibition of proliferation of the gastric carcinoma cell lines. Cell cycle analysis demonstrated that caudatin induced G0/G1 arrest and downregulated CDK2 levels. In contrast, the expression of the p21 protein was increased. AGS cells treated with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase-3, -8, -9 and PARP. Western blot analysis and immunocytochemical staining showed that caudatin induced a reduction in β-catenin expression and this reduction was due to proteosome-mediated degradation. This reduction in β-catenin activation was due to the downregulation of its downstream targets cyclinD1 and c-MYC in all gastric carcinoma cell lines. Furthermore, we demonstrated that gastric adenocarcinoma tissues and AGS cells exhibited abnormal expression of miR-372. Additionally, caudatin downregulated the expression of oncomir miR-372 and miR-21, and upregulated tumor suppressor let-7a miRNA expression. These data revealed that inhibition of Wnt/β-catenin signaling is a novel mechanism of action for caudatin during therapeutic intervention in gastric cancers. IntroductionGastric cancer is one of the most common malignancies and the second leading cause of cancer-related mortality worldwide.Surgery and systemic treatment regimens in combination with radiotherapy and chemotherapy are able to cure this malignancy in the majority of cases. Unfortunately, the young age of typical gastric cancer patients further enhances the time at risk for the side effects of these therapies. Delayed toxicity and the development of secondary malignancies are a serious concern for the current anti-neoplastic armamentarium (1,2). Therefore, it is urgent to further characterize the entity of gastric tumors to better understand and predict their biological behaviors and to identify novel high efficient and low toxic therapeutic agents for the treatment of gastric cancer in clinical practice (3).Modern pharmacologic study proves that C-21 steroidal glycosides are important biological active compounds, which are widely found in the plants of the Asclepiadaceae family and exhibit extensive pharmacological effects such as inhibition of proliferation, induction of apoptosis and inhibition of the invasion of tumor cells (4,5). Caudatin, a C-21 steroidal glycoside, is mainly isolated from the root of Cynanchum bungei Decne in China. Recent studies demonstrated that caudatin induced the apoptosis of HepG2 cells or the SMMC772 cell line (6,7). Wang et al (8) found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication. Furthermore, caudatin as a prospective anti-HCC drug with the mechanism...

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“…In our previous study, we isolated four new C 21 -steroidal glycosides from the roots of Cynanchum auriculatum and reported the anticancer activity of auriculoside A (AA) which was the most active of the four (8,11,12). In the present study, CG, a C 21 -steroidal glycoside first isolated by Warashina et al in 1995, demonstrated greater cytotoxic effects than AA.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and apoptosis-inducing properties of a C21-steroidal glycoside isolated from the roots of Cynanchum auriculatum

Wang

Yang

et al. 2013

Oncology Letters

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The present study aimed to investigate the anti-cancer effect of a C21-steroidal glycoside (CG) isolated from the roots of Cynanchum auriculatum. CG was able to inhibit the growth of human cancer cells (SGC-7901 cells) in a concentration and time-dependent manner in vitro. SGC-7901 cells exposed to CG (10.8 and 21.6 μM) exhibited typical morphological apoptosis characteristics, such as nuclear-chromatin condensation and apoptotic body formation. Flow cytometric analysis showed that after treatment with CG at 10.8 and 21.6 μM for 24 h, the percentage of apoptotic cells increased to 30.4 and 43.2%, respectively, while the number of cells in the G0/G1, S and G2/M phases of the cell cycle decreased (P<0.05). Furthermore, treatment with CG at a concentration of 21.6 μM for 24 h significantly increased the expression of caspase-3 and the activity of caspase-3 was increased ∼3-fold in SGC-7901 cells. These results suggest that CG is the active anticancer component of the total C21-glycosides of the roots of Cynanchum auriculatum which is able to inhibit the growth of cancer cells and induce cancer cell apoptosis through caspase-3-dependent pathways.

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Caudatin induces cell cycle arrest and caspase-dependent apoptosis in HepG2 cell

Cited by 29 publications

References 23 publications

Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells

Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

Cytotoxic and apoptosis-inducing properties of a C21-steroidal glycoside isolated from the roots of Cynanchum auriculatum

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