Tetrandrine Induces Apoptosis and Triggers Caspase Cascade in Human Bladder Cancer Cells

Li, Xudong; Su, Bin; Liu, Runming; Wu, Dapeng; He, Dalin

doi:10.1016/j.jss.2010.10.034

Cited by 58 publications

(52 citation statements)

References 27 publications

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“…Thus, it is necessary to identify and develop new anticancer agents that will selectively target the tumor. It was reported that the induction of apoptosis through the caspase cascade triggered by tetrandrine has inhibitory effects to various tumor cells (20,21,27,37). Many studies have demonstrated that tetrandrine has pharmacologic potential in cancer therapy but to date the effects of tetrandrine on human oral cancer is little known and have not been identified and reported in oral cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Huang¹,

Lien

Meng

et al. 2013

International Journal of Oncology

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Abstract. Numerous studies have demonstrated that autophagy is associated with cancer development. Thus, agents to induce autophagy could be employed in some cases for the treatment of cancer. Our results showed that tetrandrine significantly decreased the viability of SAS cells in a concentration-and time-dependent manner. Tetrandrine induced nuclear condensation, demonstrated by DAPI staining. The early events in apoptosis analysed by Annexin V/PI staining indicated that the percentage of cells staining positive for Annexin V was slightly increased in SAS cells with tetrandrine treatment but was much lower following bafilomycin A1 pre-treatment. Tetrandrine caused AVO and MDC induction in SAS cells in a concentration-dependent manner by fluorescence microscopy. Tetrandrine also caused LC-3 expression in SAS cells in a time-dependent manner. Our results show that tetrandrine treatment induced the levels of cleaved caspase-3 in a concentration-and time-dependent manner. Tetrandrine treatment induced the levels of LC-3 II, Atg-5, beclin-1, p-S6, p-ULK, p-mTOR, p-Akt (S473) and raptor. Tetrandrine decreased cell viability, but bafilomycin A1, 3-MA, chloroquine and NAC protected tetrandrine-treated SAS cells against decrease of cell viability. Atg-5, beclin-1 siRNA decreased tetrandrineinduced cleaved caspase-3 and cleaved PARP in SAS cells and protected tetrandrine-treated SAS cells against decrease in cell viability. Chloroquine, NAC and bafilomycin A1 also decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells. Our results indicate the tetrandrine induces apoptosis and autophagy of SAS human cancer cells via caspase-dependent and LC3-I and LC3-II-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

“…Tetradine induced apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma HCC cells (35,36). Recently, it was reported that tetrandrine induced apoptosis and triggers caspase cascade in human bladder cancer cells (37).…”

Section: Introductionmentioning

confidence: 98%

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Huang¹,

Lien

Meng

et al. 2013

International Journal of Oncology

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“…It has been shown that tumor cell apoptosis caused by tetrandrine exhibits inhibitory effects on various types of tumor cell (24)(25)(26)(27)(28)(29). The results of the present study indicated that tetrandrine had no cytotoxic effect on the HT29 cells, however, the anti-metastatic effect of tetrandrine on EGF-induced HT29 cancer cells was observed, and the underlying molecular signaling was evaluated.…”

Section: Discussionmentioning

confidence: 58%

“…Tetrandrine has been shown to have broad pharmacological actions (20)(21)(22). Several reports have indicated that tetrandrine presents potent anticancer effects on multiple cancer cells in vitro (23)(24)(25)(26)(27)(28)(29). Tetrandrine retards Wnt/β-catenin signaling and inhibits tumor growth of HCT116 human colorectal cancer (24).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

Horng

Yang

Chiang³

et al. 2015

Molecular Medicine Reports

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Abstract.Tetrandrine has been shown to reduce cancer cell proliferation and to inhibit metastatic effects in multiple cancer models in vitro and in vivo. However, the effects of tetrandrine on the underlying mechanism of HT29 human colorectal adenocarcinoma cell metastasis remain to be fully elucidated. The aim of the present study was focused on tetrandrine-treated HT29 cells following epidermal growth factor (EGF) treatment, and Transwell, gelatin zymography, gene expression and immunoblotting assays were performed to investigate metastatic effects in vitro. Tetrandrine was observed to dose-dependently inhibit EGF-induced HT29 cell invasion and migration, however, no effect on cell viability occurred following exposure to tetradrine between 0.5 and 2 µM. Tetrandrine treatment inhibited the enzymatic activity of matrix metalloprotease (MMP)-2 and MMP-9 in a concentration-dependent manner. The present study also found a reduction in the mRNA expression levels of MMP-2 and MMP-9 in the tetrandrine-treated HT29 cells. Tetrandrine also suppressed the phosphorylation of EGF receptor (EGFR) and its downstream pathway, including phosphoinositide-dependent kinase 1, phosphatidylinositol 3-kinase and phosphorylated AKT, suppressing the gene expression of MMP-2 and MMP-9. Furthermore, tetrandrine triggered mitogen-activated protein kinase signaling through the suppressing the activation of phosphorylated extracellular signal-regulated protein kinase. These data suggested that targeting EGFR signaling and its downstream molecules contributed to the inhibition of EGF-induced HT29 cell metastasis caused by tetrandrine, eventually leading to a reduction in the mRNA and gelatinase activities of MMP-2 and MMP-9, respectively. IntroductionEpidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases (1), and EGFR activation by ligand binding stimulates multiple signals, including phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinases (MAPKs) and nuclear factor-κB pathways, ultimately resulting in cellular proliferation, survival, angiogenesis invasion and metastasis (2,3). Abnormal protein activity and/or expression levels of EGFR have been correlated with the etiology of several types of human cancer, including colorectal cancer (4,5), non-small cell lung cancer (6,7), breast cancer (8,9), head and neck squamous cell carcinoma (10,11), pancreatic cancer (12) and brain cancer (13). EGFR-targeted therapy has been validated in human colorectal cancer (14), and the chemotherapeutics include pharmacological agents, including cetuximab (Erbitux), which is an EGFR inhibitor (15). EGFR acts to bind an EGFR-selective ligand activated by epidermal growth factor (EGF), transforming growth factor-α, amphiregulin or neuregulin, finally leading to cell proliferation, invasion and the inhibition of apoptosis (15)(16)(17).Tetrandrine is a bisbenzylisoquinoline alkaloid, which is isolated from the dried root of Stephania tetrandra of the

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“…1), a bis-benzylisoquinoline alkaloid isolated from the Chinese herb 'Han-Fang-Ji' (Radix Stephania tetrandra S. Moore), has been found to have immunosuppressive, free radical scavenging and anti-inflammatory activities (4-6). Furthermore, many recent studies have shown that TET exerts antitumor effects (7,8). In addition to inhibiting proliferation and inducing apoptosis of several cancer types, TET has exhibited potential as an adjunct to chemotherapy in many drug-resistant cancer cell lines (9,10).…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

et al. 2012

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Abstract. Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents to control esophageal cancer. Herein, we investigated that the effect and mechanism of tetrandrine (TET) in the human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP. The human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP was isolated by stepwise selection in increasing concentrations of cisplatin. The CCK-8 method was carried out to measure the cell viability when cells were exposed to TET with or without cisplatin, and the IC 50 and resistance index (RI) of cisplatin was then calculated. Real-time RT-PCR and western blotting were used to detect the mRNA and protein expression of multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), respectively. Flow cytometry was adopted to determine CMFDA efflux and cell apoptosis, respectively. The resulting cell line YES-2/ DDP was 16.4-fold resistant to cisplatin, the cytotoxicity of cisplatin to YES-2/DDP cells was enhanced by TET in a dosedependent manner. Further, it was found that the expression of MDR1 and BCRP was similar in different treated cells. In contrast, the expression of MRP1 was markedly increased in YES-2/DDP cells, which was dose-dependently decreased by TET. In agreement with the results, MRP1 activity was also reversed by TET. In conclusion, TET possesses a reversal effect on drug resistance in YES-2/DDP cells through downregulation of MRP1, and has the potential to be an adjunct to chemotherapy for esophageal cancer. IntroductionChemotherapy is regarded as an important line of defense against esophageal cancer which is one of the most aggressive and lethal malignancies. However, on account of drug resistance especially multi-drug resistance (MDR), only a limited proportion of cancer patients respond favorably to commonly used chemotherapeutic drugs (1). With respect to the mechanisms of drug resistance, ATP-binding cassette (ABC) transporters, such as ABCB1/multidrug resistance 1 (MDR1), ABCC1/multidrug resistance-associated protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP), mediate energy-dependent drug efflux and play a main role in chemoresistance (2,3). Therefore, it seems imperative to find new drugs or methods especially targeting ABC transporters to reverse tumor drug-resistance.Tetrandrine (TET) (Fig. 1), a bis-benzylisoquinoline alkaloid isolated from the Chinese herb 'Han-Fang-Ji' (Radix Stephania tetrandra S. Moore), has been found to have immunosuppressive, free radical scavenging and anti-inflammatory activities (4-6). Furthermore, many recent studies have shown that TET exerts antitumor effects (7,8). In addition to inhibiting proliferation and inducing apoptosis of several cancer types, TET has exhibited potential as an adjunct to chemotherapy in many drug-resistant cancer cell lines (9,10). However, it remains unclear whether TET can reverse ABC transporter-mediated drug efflux. Moreover, it is als...

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Tetrandrine Induces Apoptosis and Triggers Caspase Cascade in Human Bladder Cancer Cells

Cited by 58 publications

References 27 publications

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

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