Tetrandrine-induced apoptosis is mediated by activation of caspases and PKC-δ in U937 cells

Jang, Byeong‐Churl; Lim, Ki-Jo; Paik, Jihye; Cho, Jae-We; Baek, Won-Ki; Suh, Min-Ho; Park, Jae-Bok; Kwon, Tae Chan; Park, Jong‐Wook; Kim, Sang-Pyo; Shin, Dong‐Hoon; Song, Dae‐Kyu; Bae, Jae‐Hoon; Mun, Kyo‐Cheol; Suh, Seong-Il

doi:10.1016/j.bcp.2004.01.018

Cited by 54 publications

(47 citation statements)

References 42 publications

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“…The volume of the tumor was calculated from the formula V 5 1/2 (d1 3 d2 3 d3), where d1, d2 and d3 were mutually perpendicular diameters measured by calipers. Each point represents the average volume (cm 3 ) of the tumors for each of these groups. Daily average tumor volumes for each group were compared throughout the course of the experiment using Analysis of variance (ANOVA) and the post hoc Scheffe's multiple comparison.…”

Section: Effect Of Tetrandrine On Intracerebral Gliomasmentioning

confidence: 99%

“…[2][3][4] It suppresses T and B cells and inhibits the production of cytokines such as histamine, prostaglandins and tumor necrosis factor-a. 5,6 Tetrandrine has been used for treatment of silicosis and can suppress inflammatory reactions associated with rheumatoid arthritis and uveitis or hepatitis in animals that is provoked by bovine serum albumin, interleukin-1 (IL-1) or endotoxin.…”

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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%

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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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Section: Effect Of Tetrandrine On Intracerebral Gliomasmentioning

confidence: 99%

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confidence: 99%

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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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“…However, others showed that tetrandrine-induced apoptosis associated with oxidative stress and MPT induction in both cancer cell lines (Jin et al, 2002;Oh and Lee, 2003;Jang et al, 2004) and rat primary hepatocytes (Yan et al, 2006). This discrepancy suggests that tetrandrine-induced apoptosis is due to factors other than a direct immediate interaction of tetrandrine with isolated mitochondria.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of tetrandrine include induction of apoptosis in tumor cells, reversal of multidrug resistance to other anti-cancer drugs, sensitization of tumor cells to radiation, reduction of radiation injury in normal mononuclear cells and skin, and inhibition of angiogenesis (Yu-Jen, 2002). Recent studies have shown that tetrandrine-induced apoptosis in Neuro 2a mouse neuroblastoma cells, rat glioma cells (C-6) (Jin et al, 2002), human hepatoblastoma (Hep G2) (Oh and Lee, 2003), human leukaemia cells (U937) (Jang et al, 2004), and rat primary hepatocytes (Yan et al, 2006) is associated with ROS generation and cytochrome c release, thus suggesting that mitochondria are primarily involved. However, these studies seem to be controversial with those published by others (Seow et al, 1988;Matsuno et al, 1990;Castranova, 1994;Hui et al, 1996;Shen et al, 1999aShen et al, ,b, 2001Koh et al, 2003;Sekiya et al, 2005;Ren et al, 1995;Liu et al, 2004) demonstrating that tetrandrine protects several types of cells from oxidative stress by acting as a ROS scavenger.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress

et al. 2006

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The effects of tetrandrine (6,6 0 , 7,12-tetramethoxy-2, 2 0 -dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/ mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca 2+ -induced opening of MPT pore, and inhibited the inner membrane anion channel activity, not significantly affecting the mitochondrial bioenergetics. High tetrandrine concentrations (100-300 nmol/mg protein) stimulated succinate-dependent state 4 respiration, while some inhibition was observed for state 3 and p-trifluoromethoxyphenylhydrazone-uncoupled respirations. The respiratory control ratio and the transmembrane potential were depressed but the adenosine diphosphate to oxygen (ADP/O) ratio was less affected. A slight increase of the inner mitochondrial membrane permeability to H + and K + by tetrandrine was also observed. It was concluded that low concentrations of tetrandrine afford protection against liver mitochondria injury promoted by oxidative-stress events, such as hydrogen peroxide production, lipid peroxidation, and induction of MPT. Conversely, high tetrandrine concentrations revealed toxicological effects expressed by interference with mitochondrial bioenergetics, as a consequence of some inner membrane permeability to H + and K + and inhibition of the electron flux in the respiratory chain. The direct immediate protective role of tetrandrine against mitochondrial oxidative stress may be relevant to clarify the mechanisms responsible for its multiple pharmacological actions.

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Tetrandrine, a novel inhibitor of ether‐à‐go‐go‐1 (Eag1), targeted to cervical cancer development

Wang

Chen

et al. 2018

Journal Cellular Physiology

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Mortality-to-incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether-à-go-go-1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration-dependent manner (IC 50 of 69.97 ± 5.2 μM), and the amino acids Ile 550 , Thr 552 , and Gln 557 in the Eag1 C-linker domain were critical for tetrandrine's inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentrationdependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell-transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction-induced diseases.

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Tetrandrine-induced apoptosis is mediated by activation of caspases and PKC-δ in U937 cells

Cited by 54 publications

References 42 publications

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress

Tetrandrine, a novel inhibitor of ether‐à‐go‐go‐1 (Eag1), targeted to cervical cancer development

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