The novel targets for anti-angiogenesis of genistein on human cancer cells

Su, Shih Bin; Yeh, Trai Ming; Chuang, Woei Jer; Ho, Chung Liang; Chang, Kee-Lung; Cheng, Hsiu-Chung; Liu, Hsiao Sheng; Cheng, Hong; Hsu, Pei Yin; Chow, Nan Haw

doi:10.1016/j.bcp.2004.09.025

Cited by 123 publications

(72 citation statements)

References 42 publications

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“…Among soy isoflavones, the chemopreventive property of genistein has been the subject of extensive in vitro and in vivo research. The experimental studies have shown that genistein inhibits the growth of bladder cancer cells by inhibiting proliferation in vitro (16,17,(26)(27)(28) and in vivo (16,17,28), inducing apoptosis in vitro (17) and in vivo (17), and inhibiting angiogenesis in vitro (28,29) and in vivo (20,28). In this report, we found that both genistin and SPC significantly induced bladder tumor cell apoptosis and inhibited tumor angiogenesis in vivo (Table 1).…”

Section: Discussionsupporting

confidence: 50%

“…These functions include inhibition of tyrosine kinase activities (30) and epidermal growth factor receptor signal transduction pathways (27); induction of G 2 -M cell cycle arrest and inhibition of cdc-2 kinase activity (16); down-regulation of the angiogenic factors vascular endothelial growth factor (28, 31), platelet-derived growth factor (28), tissue factor (28), urokinase plasminogen activator (28), and matrix metalloproteinases (28); and up-regulation of angiogenesis inhibitors plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1 (28). Our in vitro studies in this report showed that genistein inhibited bladder cancer cell proliferation by inducing G 2 -M arrest via modulation of G 2 -M phase-related regulators, such as cyclin B1, Cdk-1, and Cdc-25C (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Soy Phytochemicals Prevent Orthotopic Growth and Metastasis of Bladder Cancer in Mice by Alterations of Cancer Cell Proliferation and Apoptosis and Tumor Angiogenesis

et al. 2006

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A role of dietary bioactive components in bladder cancer prevention is biologically plausible because most substances or metabolites are excreted through the urinary tract and are consequently in direct contact with the mucosa of the bladder. We first determined antigrowth activity of genistein against poorly differentiated 253J B-V human bladder cancer cells in vitro. Genistein inhibited the cell growth in a time-and dosedependent manner via G 2 -M arrest, down-regulation of nuclear factor KB (NF-KB), and induction of apoptosis. We also evaluated both genistin, which is a natural form of genistein, and the isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis of 253J B-V tumors in an orthotopic tumor model. Mice treated with genistin and SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P < 0.01) associated with significant down-regulation of NF-KB expression in tumor tissues and reduction of circulating insulin-like growth factor-I levels, suggesting that SPC may contain other bioactive ingredients that have antimetastatic activity. The results from our studies suggest that further clinical investigation should be warranted to apply soy phytochemicals, such as SPC, as a potent prevention regimen for bladder cancer progression. This orthotopic human bladder tumor model also provides a clinically relevant experimental tool for assessing potential preventive activity of other dietary components against bladder tumor growth and metastasis.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Soy Phytochemicals Prevent Orthotopic Growth and Metastasis of Bladder Cancer in Mice by Alterations of Cancer Cell Proliferation and Apoptosis and Tumor Angiogenesis

et al. 2006

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“…On the other hand, there was an upregulation of angiogenesis inhibitors: plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1. 59 ABCG1 gene, whose expression was also found to correlate with GI 50 values for ARSs encodes an ATPdependent transporter that is downregulated by the antiangiogenic antioxidants N-acetyl cysteine and (À)-epigallocatechin gallate. 60 It is intriguing that many chemopreventive drugs exert antiangiogenic features as ARSs do.…”

Section: Discussionmentioning

confidence: 98%

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

et al. 2006

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Artemisinin (ARS) and its derivatives are used for the second-line therapy of malaria infections with Plasmodium falciparum and P. vivax. ARSs also reveal profound antitumor activity in vitro and in vivo. In the present investigation, we correlated the mRNA expression data of 89 angiogenesis-related genes obtained by microarray hybridization from the database of the US National Cancer Institute with the 50% growth inhibition concentration values for eight ARSs (ARS, arteether (ARE), artesunate (ART), artemisetene, arteanuine B, dihydroartemisinylester stereoisomers 1 and 2). The constitutive expression of 30 genes correlated significantly with the cellular response to ARSs. By means of hierarchical cluster analysis and cluster image mapping expression, profiles were identified that determined significantly the cellular response to ART, ARE, artemether and dihydroartemisinylester stereoisomer 1. We have exemplarily validated the microarray data of six out of these 30 genes by realtime RT-PCR in seven cell lines. The fact that sensitivity and resistance of tumor cells could be predicted by the mRNA expression of angiogenesisrelated genes indicate that ARSs reveal their antitumor effects at least in part by inhibition of tumor angiogenesis. As many chemopreventive drugs exert antiangiogenic features, ARSs might also be chemopreventive in addition to their cytotoxic effects.

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“…Genistein has been known to inhibit TGF-β signaling, and therefore inhibit angiogenesis [116]. Further evidence in support of soy-based foods as natural dietary inhibitors of tumor angiogenesis was reported in a study by Su et al [117]. The efficacy of soy isoflavones on angiogenesis inhibition in vivo was examined by nude mice xenograft and chick chorioallantoic membrane bioassay.…”

Section: Effects On the Inhibition Of Angiogenesis And Metastasismentioning

confidence: 98%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

560

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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The novel targets for anti-angiogenesis of genistein on human cancer cells

Cited by 123 publications

References 42 publications

Soy Phytochemicals Prevent Orthotopic Growth and Metastasis of Bladder Cancer in Mice by Alterations of Cancer Cell Proliferation and Apoptosis and Tumor Angiogenesis

Soy Phytochemicals Prevent Orthotopic Growth and Metastasis of Bladder Cancer in Mice by Alterations of Cancer Cell Proliferation and Apoptosis and Tumor Angiogenesis

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

Multi-targeted therapy of cancer by genistein

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