Induction of apoptosis in human leukemic U937 cells by tetrandrine

Lai, Yuen Liang; Chen, Yu-Jen; Wu, Tsu Yen; Wang, Sheng Yuan; Chang, Kao‐Shuo; Chung, Chong Hung; Chen, Mong Liang

doi:10.1097/00001813-199801000-00009

Cited by 44 publications

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“…Our LC 50 value is comparable with previously reported LC 50 values for tetrandrine against breast cancer, lung cancer, neuroblastoma, Burkitt's lymphoma, hepatoma and leukemia. 3,[12][13][14][15][16]33 Defective control of apoptosis plays a central role in tumor pathogenesis, 34 so we also studied the effect of tetrandrine on induction of glioma cell apoptosis. Our results show that tetrandrine induces apoptosis in RT-2 glioma cells as has been observed in other cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Recent research has shown that tetrandrine inhibits the proliferation and induces the apoptosis of several cancers, including breast cancer, lung cancer, neuroblastoma, Burkitt's lymphoma, hepatoma and leukemia. 3,[12][13][14][15][16] The mechanisms of these antitumor effects are not fully understood. Tetrandrine increases the expression of p53, p21 and bax, causes p53 nuclear translocation, induces pRB hypo-phosphorylation, increases cell apoptotic signals such as Apo-1 (also called CD95 or FasR), induces the Cdk inhibitor p1, decreases the expression of cyclin D1, increases the release of mitochondrial cytochrome c, activates caspases-3, -8 and -9, increases cleavage of PARP (poly(ADP-ribose) polymerase) and reduces Bcl-X L .…”

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confidence: 99%

“…18 We hypothesized that tetrandrine might inhibit the proliferation of glioma cells because ion channels in unexcitable cells are involved in proliferation and volume regulation 20 and tetrandrine induces cellular apoptosis via inhibition of BK channels, which reduces K 1 efflux and depolarization. 6,13,15 There are no previous reports on the effects of tetrandrine on glioma cell proliferation. One publication reported that tetrandrine eliminates radiation-induced cell cycle perturbation and enhances the radiosensitivity of human glioblastoma cells.…”

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Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Chen

Tseng

2009

Intl Journal of Cancer

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Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers, but its effects on gliomas are unknown. In this study, we investigated the effects of tetrandrine on the growth and angiogenesis of rat RT-2 gliomas. We treated RT-2 glioma cells with tetrandrine and then measured cytotoxicity, apoptosis and expression of vascular endothelial growth factor (VEGF). We also examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein endothelial cells and the effects of tetrandrine on the in vivo angiogenesis. Tumor size and animal survival were followed in tetrandrine-treated rats with subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrinetreated gliomas was followed to study its effect on glioma-induced angiogenesis. Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a concentration-and time-dependent manner. Tetrandrine also inhibited the expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304 cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had significant antitumor effects on subcutaneous tumors and led to slower tumor growth rate, longer animal survival time and higher animal survival (p < 0.05). Tetrandrine also affected intracerebral tumors and prolonged animal survival (p < 0.05) without affecting survival rate. Immunohistochemical analyses showed that the subcutaneous gliomas from tetrandrine-treated rats had fewer microvessel densities than control rats (p 5 0.01). The results demonstrate that tetrandrine is cytotoxic to RT-2 glioma cells, has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas. Tetrandrine has potential as a treatment for gliomas.

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Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Chen

Tseng

2009

Intl Journal of Cancer

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“…It was reported that tetrandrine mediated apoptosis in human leukemic cells and colon cancer cells. 18,19 To determine whether tetrandrine induces apoptosis of human HCC cells, dose-dependent response and time-course experiments of tetrandrine treatment were performed. Cell viability assay showed that tetrandrine induced Huh7, HepG2 and BEL7402 cell death in a concentration-dependent and dynamic manner, and Huh7 cells were more sensitive to tetrandrine treatment than HepG2 and BEL7402 cells (Figs.…”

Section: Tetrandrine Induces Apoptosis Of Hcc Cells In a Dosedependenmentioning

confidence: 99%

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Liu¹,

Gong²,

Mao³

et al. 2011

Intl Journal of Cancer

126

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Tetrandrine, a bisbenzylisoquinoline alkaloid component of broadly used traditional Chinese medicine, has antitumor effects against some cancers. In our study, we investigated the effects of tetrandrine on the human hepatocellular carcinoma (HCC) in vitro and in vivo. The results showed that tetrandrine effectively induced apoptosis of liver cancer cell in a dose-and time-dependent manner accompanied by alteration of cell morphology, chromatin fragmentation and caspase activation. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS), and ROS scavengers (LNAC and GSH) completely blocked the effects of tetrandrine-induced apoptosis, suggesting that the generation of ROS plays an important role in tetrandrine-induced apoptosis. Although the activities of JNK and ERK were inhibited significantly by tetrandrine treatment, JNK and ERK are not involved in the tetrandrine-induced apoptosis. In contrast, Akt activity was found to be closely related to tetrandrine-induced apoptosis. The data demonstrated that Akt activity inhibitor LY294002 synergistically promoted tetrandrine-induced apoptosis of HCC, whereas ectopic expression of Akt contrastly abrogated partial of the tetrandrine-induced apoptosis. These data suggest that Akt signal is the downstream event of ROS generation in the tetrandrine-induced HCC cell apoptosis. Moreover, the results of xenograft in nude mice were consistent with that of the in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of HCC as a regulator of ROS/Akt pathway.

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“…Several studies recently have shown that tetrandrine possesses antitumor activity in cultured tumor cells and animal models (19 -27). Tetrandrine induces G 1 -phase arrest in cells containing wild-type p53 (20,25) and apoptosis in p53 wild-type and null cells (20,22,25). However, the molecular mechanisms by which tetrandrine induces G 1 -phase arrest remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine Induces Early G1 Arrest in Human Colon Carcinoma Cells by Down-Regulating the Activity and Inducing the Degradation of G1-S–Specific Cyclin-Dependent Kinases and by Inducing p53 and p21Cip1

et al. 2004

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Tetrandrine is an antitumor alkaloid isolated from the root of Stephania tetrandra. We find that micromolar concentrations of tetrandrine irreversibly inhibit the proliferation of human colon carcinoma cells in MTT and clonogenic assays by arresting cells in G 1 . Tetrandrine induces G 1 arrest before the restriction point in nocodazole-and serum-starved synchronized HT29 cells, without affecting the G 1 -S transition in aphidicolin-synchronized cells. Tetrandrine-induced G 1 arrest is followed by apoptosis as shown by fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated nick end labeling, and annexin V staining assays. Tetrandrine-induced early G 1 arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21Cip1 in wild-type p53 HCT116 cells. Collectively, these results show that tetrandrine arrests cells in G 1 by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21Cip1 .

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Induction of apoptosis in human leukemic U937 cells by tetrandrine

Cited by 44 publications

References 0 publications

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Tetrandrine Induces Early G1 Arrest in Human Colon Carcinoma Cells by Down-Regulating the Activity and Inducing the Degradation of G1-S–Specific Cyclin-Dependent Kinases and by Inducing p53 and p21Cip1

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