Inhibitory Effects of Tetrandrine and Related Synthetic Compounds on Angiogenesis in Streptozotocin-Diabetic Rodents.

Kobayashi, Shogo; Kimura, Ikuko; Fukuta, Mizuki; Kontani, Hitoshi; Inaba, Kazuhiko; Niwa, Masashi; Mita, Shiro; Kimura, Masayasu

doi:10.1248/bpb.22.360

Cited by 26 publications

(25 citation statements)

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“…24 Tetrandrine inhibits choroidal angiogenesis and air-pouch granuloma angiogenesis in diabetic rodents and fetal bovine serum-, IL-1a-, VEGF-or platelet-derived growth factor (PDGF)-BB-stimulated tube formation in vascular endothelial cells. 24 There are no previous reports on the effect of tetrandrine on angiogenesis in malignant tumors. Angiogenesis can promote tumor growth and increase the number of channels for tumor cell metastases.…”

Section: Discussionmentioning

confidence: 99%

“…In Group D, 70% of the rats had longterm survival and the survival time of rats that ultimately died was 68 days longer. The survival rate of Group D rats was significantly higher than that of Groups A, B and C (Group D vs. Group A or B, 24 or 72 hr, the apoptosis fraction of the RT-2 glioma cells was analyzed using a flow-activated cell sorter (FACS). Each point is the average of 3 independent trials (9 determinations for each concentration) and presented as mean 6 standard deviation.…”

Section: Effect Of Tetrandrine On Subcutaneous Gliomasmentioning

confidence: 99%

“…23 Another recent study reported that tetrandrine inhibits adjuvant-induced angiogenesis in vitro and suppress angiogenesis in streptozotocin-induced diabetic rodents. 24 Heretofore, no studies have investigated the effects of tetrandrine on the neovascularization of tumors.…”

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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: Discussionmentioning

confidence: 99%

Section: Effect Of Tetrandrine On Subcutaneous Gliomasmentioning

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 have been demonstrated to inhibit lipid peroxidation and platelet aggregation and reduces ischemia/reperfusion injury (28)(29)(30) and tetrandrine suppressed T and B cells and inhibited the production of cytokines (29). It was reported that tetrandrine is cytotoxic to RT-2 glioma cells and it has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas (31)(32)(33)(34). Tetradine induced apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma HCC cells (35,36).…”

Section: Introductionmentioning

confidence: 99%

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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“…4) Tetrandrine inhibits precapillary formation of vascular endothelial cells and neovascularization of cultured choroidal explants in STZ-diabetic rats, 8,9) but does not affect hyperglycemia in diabetic mice.…”

Section: )mentioning

confidence: 99%

Combined Effects of Fangchinoline from Stephania Tetrandra Radix and Formononetin and Calycosin from Astragalus membranaceus Radix on Hyperglycemia and Hypoinsulinemia in Streptozotocin-Diabetic Mice

Nomura

Takahashi-Nishioka

et al. 2007

Biological & Pharmaceutical Bulletin

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Boi-ogi-to (Fang-ji-huang-qi-tang) is a traditional prescription in Kampo medicine and consists of Stephania tetrandra Radix (Stephania), Astragalus membranaceus BUNGE Radix (Astragali), Atractylodes Lancea Rhizoma, Glycyrrhizae Radix, Zingiberis Rhizoma and Zizyphi Fructus. Boi-ogi-to has long been used clinically in the treatment of arthritis and edema in China and Japan. It also improves abnormal glucose and lipid metabolism in obese diabetic patients. 1) We have reported that Boi-ogi-to increases blood insulin and decreases blood glucose levels in streptozotocin (STZ)-diabetic mice. The anti-hyperglycemic and anti-hypoinsulinemic actions of Boi-ogi-to depend on the combination of Stephania and Astragali.2) Astragali does not have a direct anti-hyperglycemic effect, but potentiates the actions of Stephania on blood levels of both glucose and insulin in STZ-induced diabetes. 3,4) In addition, Stephania suppresses abnormal choroidal and retinal neovascularization in STZ-induced diabetes in vitro and in vivo. 5)Stephania contains many bis-benzylisoquinoline-type constituents, such as tetrandrine and fangchinoline.6,7) Fangchinoline significantly improves hyperglycemia of STZ-diabetic mice.4) Tetrandrine inhibits precapillary formation of vascular endothelial cells and neovascularization of cultured choroidal explants in STZ-diabetic rats, 8,9) but does not affect hyperglycemia in diabetic mice.4) Fangchinoline and tetrandrine show different anti-inflammatory actions via inhibition of cyclooxygenase and interleukin-5 activities.10) In other studies, fangchinoline and tetrandrine were found to have similar inhibitory activities on both angiotensin I converting enzyme, 6,7) and induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha by Staphylococcus aureus Cowan 1-stimulated human peripheral blood mononuclear cells. 11)Astragali contains many isoflavones and isoflavonoids, such as formononetin, calycosin and ononin, and many saponins, such as astragaloside IV, astragaloside II, astragaloside I, and acetylastragaloside I.12) Formononetin significantly reduces arachidonic acid release and production of nitric oxide in lipopolysaccharide activated RAW 264.7 macrophages.13) It also shows estrogen receptor agonistic activity in human breast cell line MCF-7.14,15) Formononetin and calycosin activate the peroxisome proliferator-activated receptors (PPAR) alpha and gamma. The action of formononetin is more potent than that of calycosin.16) Calycosin is a vasorelaxant and is a noncompetitive Ca 2ϩ channel blocker, whose action is endothelium-independent and unrelated to intracellular Ca 2ϩ release. The effect of calycosin on Ca 2ϩ channel blockade may be different from that of dihydropyridines.17) In addition, formononetin, calycosin and ononin all inhibit glutamate-induced cell damage by increasing endogenous antioxidant and stabilizing cell membrane structures. 18)In the present study, the combined effects of fangchinoline with formononetin, calycosin and ononin on the blood levels of glucos...

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Inhibitory Effects of Tetrandrine and Related Synthetic Compounds on Angiogenesis in Streptozotocin-Diabetic Rodents.

Cited by 26 publications

References 1 publication

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

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

Combined Effects of Fangchinoline from Stephania Tetrandra Radix and Formononetin and Calycosin from Astragalus membranaceus Radix on Hyperglycemia and Hypoinsulinemia in Streptozotocin-Diabetic Mice

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