Suppression of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle cells.

Zou, Jiangang; Ya, Huang; Chen, Qi; Wang, Nan; Cao, Ke; Hsieh, Tze Chen; Wu, Jingwan

doi:10.3892/ijo.15.4.647

Cited by 31 publications

(43 citation statements)

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“…In agreement with studies by others (15,16,(25)(26)(27)(28)30), trans-resveratrol has been found to inhibit in a dose-and time-dependent manner cell growth both in normal fibroblasts and in fibrosarcoma cells. An antiproliferative activity comparable to that of trans-resveratrol has been observed only for derivative IV.…”

Section: Discussionsupporting

confidence: 78%

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Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol

Stivala¹,

Savio²,

Carafoli³

et al. 2001

Journal of Biological Chemistry

450

344

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Resveratrol (3,4,5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine, which shows antioxidant and antiproliferative activities. In this study we have investigated whether these properties are dependent on similar or different structural determinants of the molecule. To this purpose, resveratrol derivatives, in which all or each single hydroxylic function were selectively substituted with methyl groups, were synthesized. Analogues with the stilbenic double bond reduced or with the stereoisomery modified were also investigated. The antioxidant activity of these compounds was evaluated by measuring the inhibition of citronellal thermo-oxidation, or the reduction of 2,2-diphenyl-1-picrylhydrazyl radical. In addition, the protection against lipid peroxidation was determined in rat liver microsomes, and in human primary cell cultures. The antiproliferative activity was evaluated by a clonogenic assay, and by analysis of cell cycle progression and DNA synthesis. The results showed that the hydroxyl group in 4 position is not the sole determinant for antioxidant activity. In contrast, the presence of 4-OH together with stereoisomery in the trans-conformation (4-hydroxystyryl moiety) was absolutely required for inhibition of cell proliferation. Enzymatic assays in vitro demonstrated that inhibition of DNA synthesis was induced by a direct interaction of resveratrol with DNA polymerases ␣ and ␦.

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Section: Discussionsupporting

confidence: 78%

“…The proliferation of various human malignant cell lines is slowed down by resveratrol (15,16,26). The inhibition of cell growth, which has also been described in normal cells (27)(28)(29), is accompanied by the accumulation of cells in S and G 2 phases (16,26,30). Conflicting results have been reported on the induction of apoptosis by resveratrol (26,31,32).…”

mentioning

confidence: 52%

Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol

Stivala¹,

Savio²,

Carafoli³

et al. 2001

Journal of Biological Chemistry

450

344

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“…41 CD31 is involved in tube formation and inhibition of PECAM-1 suppresses tumor angiogenesis. 42,43 Thus, tetrandrine-induced reduction of CD31 expression in gliomas indicates that this drug may have antiangiogenesis effects in gliomas.…”

Section: Discussionmentioning

confidence: 99%

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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“…The mechanisms of the antitumor effects of resveratrol are not fully understood, although some mechanisms have been proposed. Resveratrol has antiestrogenic activity (15); activates the expression of p53 (18), Fas-Fas ligand system (13), and mitogen-activated protein kinase (MAPK) (19,20); inhibits p4501A1 (21), ribonucleotide reductase (22), ornithine decarboxylase (16), protein kinase C (PKC) (23), DNA polymerase (24), cyclo-oxygenase (23,25), and cell cycle progression (16,26); and induces cellular apoptosis (13,17,18,20,27). Recently, resveratrol was further demonstrated to inhibit angiogenesis, suppress capillary-like tube formation of human umbilical vein endothelial cells (HUVECs), and decrease angiogenesis in mouse lung cancer (28).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

Tseng

Lin

Chen

et al. 2004

Clinical Cancer Research

182

125

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Purpose: We wanted to investigate the antitumor effects and effect on angiogenesis of resveratrol in rat RT-2 gliomas.Experimental Design: RT-2 glioma cells were treated with resveratrol, and then cytotoxicity was assayed, apoptosis was measured by flow-activated cell sorter flow cytometry, and expression of vascular endothelial growth factor was measured by reverse transcription-PCR. Tumor size, animal survival time, and survival rate were followed in resveratrol-treated rats with s.c. or intracerebral gliomas. Furthermore, in vitro proliferation was assayed to explore the effect of resveratrol on the proliferation of ECV304 human umbilical vein endothelial cells. Expression of CD31 in resveratrol-treated gliomas was followed immunohistochemically to study the effect of resveratrol on the gliomainduced angiogenesis.Results: Resveratrol was demonstrated to exert cytotoxic effects and induce glioma cell apoptosis in a concentration-and time-dependent manner (P < 0.05). Resveratrol (40 mg/kg/day) exerted significant antitumor effects on s.c. tumors, including slower tumor growth rate, longer animal survival time, and higher animal survival rate (P < 0.05). In contrast, resveratrol affected intracerebral tumors at only an increased dose (100 mg/kg/day), prolonging animal survival (P < 0.05) without affecting survival rate. The expression of vascular endothelial growth factor in the glioma cells and the proliferation of ECV304 cells were inhibited by resveratrol in a concentration-dependent manner. Immunohistochemical analyses showed that the s.c. gliomas from resveratrol-treated rats had fewer microvessel densities than did control rats (P < 0.01).Conclusions: Resveratrol caused significant glioma cell cytotoxicity and apoptosis, exerted antitumor effects on the s.c. and intracerebral gliomas, and inhibited angiogenesis in s.c. gliomas. Thus, resveratrol might be considered a possible treatment strategy for gliomas.

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Suppression of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle cells.

Cited by 31 publications

References 0 publications

Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol

Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

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