Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis

Hseu, You Cheng; Wu, Chi‐Rei; Chang, Hsueh-Wei; Kumar, K. J. Senthil; Lin, Ming Tsan; Chen, Chih Sheng; Cho, Hsin Ju; Huang, Chuyi; Huang, Chih Yang; Lee, Hong Zin; Hsieh, Wen Tsong; Chung, Jing Gung; Wang, Hui‐Min David; Yang, Hsin Ling

doi:10.1016/j.jep.2011.04.016

Cited by 53 publications

(34 citation statements)

References 52 publications

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“…For example, Selaginella tamariscina extracts have been found to contain metastasis in lung carcinoma cells by causing decreased expression of uPA [19]. The anti-metastatic and anti-angiogenic activity of P. angulata , a well-known Chinese medicinal herb, has also been demonstrated as a consequence of its ability to inhibit uPA [4]. In another such study, Ishii et al .…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

et al. 2013

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In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 μg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study.

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Section: Introductionmentioning

confidence: 99%

Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

et al. 2013

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“…MMP-9 activation is specifically associated with tumor progression and invasion in bladder tumors [15]. In particular, recent studies have shown that many extracts isolated from plants attenuate cancer metastasis and angiogenesis via downregulating the expression of MMP-9 [16][17][18]. Therefore, inhibition of MMP-9 expression is a strategic target for the development of a therapeutic experimental model of tumor invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Activated NF-κB, in turn, modulates transcription of many target genes including MMP-9 [16]. NF-κB is a ubiquitous transcription factor that responds rapidly in mammalian cells and is strongly activated by the cytokines interleukin-1 and TNF-α under various pathological conditions [17,18].…”

Section: Discussionmentioning

confidence: 99%

Methanol Extract of Polyopes lancifolius Suppresses Tumor Necrosis Factor-α-Induced <em>Matrix</em> Metalloproteinase-9 Expression in T24 Bladder Carcinoma Cells

Jayasooriya¹,

Nam²,

Kim³

et al. 2012

Trop. J. Pharm Res

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Purpose: To investigate the effects of the methanol extract of Polyopes lancifolius (MEPL) on the expression of matrix metalloproteinase-9 (MMP-9) and invasion in T24 human bladder carcinoma cells. Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses were performed to assess the expression of MMP-9 and its regulatory proteins. MMP-9 activity was evaluated using zymography while matrigel infiltration was performed to assess T24 bladder carcinoma invasion. Electrophoretic mobility assay was used to investigate the nuclear factor-κB (NF-κB) activity. Results: The expression and activity of MMP-9 were significantly increased in response to TNF-α, but MEPL suppressed TNF-α-induced MMP-9 expression and activity. MEPL also inhibited TNF-α-induced MMP-9 expression at the transcriptional level by blocking the activation of the NF-κB signaling pathway. Furthermore, the extract suppressed TNF-α-induced phosphorylation of IκBα and consequently sustained cytosolic p65 and p50 expression. Matrigel invasion assay showed that MEPL significantly reduced TNF-α-induced invasion of T24 bladder carcinoma cells. Conclusion: Collectively, these data indicate that MEPL regulates TNF-α-induced MMP-9 expression by suppressing NF-κB activity.

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“…Tocotrienol, a member of the vitamin E family, possesses anticancer properties acting through regulating multiple signaling pathways, including anti-inflammation and antiangiogenesis [135]. The extract of Physalis angulate shows antimetastatic and antiangiogenic activity in human oral squamous carcinoma and human umbilical vein endothelial cells, probably due to its anti-inflammatory properties [136]. Indirubin inhibits inflammatory reactions by suppressing the production of interferon- γ and interleukin-6, which is a well-known inflammatory cytokine [137].…”

Section: Identifying Angiogenic Compounds From Natural Productsmentioning

confidence: 99%

From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

Hung

Zhang

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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The zebrafish (Danio rerio) has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model for in vivo high content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafish in vivo but not in vitro, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed.

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Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis

Cited by 53 publications

References 52 publications

Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

Methanol Extract of Polyopes lancifolius Suppresses Tumor Necrosis Factor-α-Induced <em>Matrix</em> Metalloproteinase-9 Expression in T24 Bladder Carcinoma Cells

From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

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