Fascaplysin exert anti-tumor effects through apoptotic and anti-angiogenesis pathways in sarcoma mice model

Yan, Xiaojun; Chen, Haimin; Lü, Xiaoling; Wang, Feng; Xu, Wei-Qun; Jin, Haixiao; Zhu, Peng

doi:10.1016/j.ejps.2011.04.018

Cited by 33 publications

(27 citation statements)

References 26 publications

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“…Moreover, it inhibited the VEGF expression and secretion by human hepatocarcinoma cells BeL-7402, suggesting that a blockade of VEGF expression could be involved in the antiangiogenic activity of this compound [87]. The down-regulation of some cell adhesion molecules and the decreased expression of endothelial cell markers-CD31 in a sarcoma mice model reinforce the conclusion that fascaplysin can inhibit angiogenesis in tumor tissue [88].…”

Section: Compounds That Inhibit the Activation Of The Angiogenic Switchsupporting

confidence: 52%

Marine Sponge Derived Antiangiogenic Compounds

Quesada

Martínez‐Poveda

Rodriguez-Nieto³

et al. 2014

Handbook of Anticancer Drugs From Marine Origin

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Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number of antiangiogenic strategies being tested in preclinical and clinical trials. Nowadays the clinical development of antiangiogenic therapies seems to be unstoppable, not only for cancer, but also for an increasing number of non-neoplasic angiogenesis-related diseases. Although most of the natural compounds previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, increasing attention is being paid to the development of marine-derived antiangiogenic agents. Marine organisms produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. There are different strategies for angiogenesis intervention, based on the modulation of any of the different steps of the angiogenic process. In this chapter, we will provide an overview of the angiogenesis inhibitors isolated from marine sponges based on the available information regarding their primary targets or mechanism of action.

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Section: Compounds That Inhibit the Activation Of The Angiogenic Switchsupporting

confidence: 52%

Marine Sponge Derived Antiangiogenic Compounds

Quesada

Martínez‐Poveda

Rodriguez-Nieto³

et al. 2014

Handbook of Anticancer Drugs From Marine Origin

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“…The marine sponge-derived bis-indole alkaloid Fascaplysin is effective against malaria [1], against bacterial, fungal, and viral infections [1], as well as against malignancy [1][2][3]. The efficacy against malignancy is at least in part due to activation of autophagy and apoptosis of tumor cells [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…The efficacy against malignancy is at least in part due to activation of autophagy and apoptosis of tumor cells [2,3]. Fascaplysin further counteracts angiogenesis by triggering apoptosis of endothelial cells [4].…”

Section: Introductionmentioning

confidence: 99%

Triggering of Suicidal Erythrocyte Death by Fascaplysin

Mischitelli

Jèmaà

Almasry

et al. 2016

Cell Physiol Biochem

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Background/Aims: The bis-indole alkaloid Fascaplysin is effective against malignancy, an effect at least partially due to stimulation of tumor cell apoptosis. Similar to apoptosis of nucleated cells, erythrocytes could enter suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress and ceramide. The present study explored, whether Fascaplysin induces eryptosis and, if so, to shed light on the cellular mechanisms involved. Methods: Flow cytometry was employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was quantified from the hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Fascaplysin (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, and significantly increased Fluo3-fluorescence, DCFDA fluorescence as well as ceramide abundance. The effect of Fascaplysin on annexin-V-binding and forward scatter was significantly blunted but not abolished by removal of extracellular Ca²⁺. Conclusions: Fascaplysin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca²⁺ entry, oxidative stress and ceramide.

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“…Fascaplysin can block VEGF, inhibit proliferation and induce apoptosis of human umbilical vein endothelial cells (HUVECs) [82]. These activities could contribute to its antiangiogenic effects shown in multiple in vitro and in vivo experimental models (Table 1) [83,84]. …”

Section: Marine-derived Protein Kinase Modulators With Antiangiogementioning

confidence: 99%

Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

Wang

Miao

2013

Marine Drugs

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Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

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Fascaplysin exert anti-tumor effects through apoptotic and anti-angiogenesis pathways in sarcoma mice model

Cited by 33 publications

References 26 publications

Marine Sponge Derived Antiangiogenic Compounds

Marine Sponge Derived Antiangiogenic Compounds

Triggering of Suicidal Erythrocyte Death by Fascaplysin

Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

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