Pharmacological evaluation of the novel thromboxane modulator BM-567 (II/II). Effects of BM-567 on osteogenic sarcoma-cell-induced platelet aggregation

Leval, Xavier de; Benoît, Valérie; Delarge, J.; Julémont, Fabien; Masereel, Bernard; Pirotte, Bernard; Merville, Marie‐Paule; David, Jean-Louis; Dogné, Jean‐Michel

doi:10.1016/s0952-3278(02)00235-1

Cited by 33 publications

(21 citation statements)

References 12 publications

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“…TXA2 (34) and ADP (35,36) are considered to be ‘soluble stimulators’ of platelet aggregation. In this study, we observed that the TXA2 and ADP pathways are activated during MCF-7 cell-induced TCIPA.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Lian

et al. 2012

Oncology Letters

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Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets. Tumor cell-induced platelet aggregation (TCIPA) contributes significantly to hematogenous metastasis; however, the molecular mechanisms involved in breast cancer TCIPA are poorly characterized. In this study, MCF-7 metastatic human breast cancer cells induced dose-dependent aggregation of washed platelets. Four major platelet activation pathways, glycoprotein (GP)-Ib-IX, GPIIb/IIIa, thromboxane (TX)-A2 and adenosine diphosphate (ADP) were activated during TCIPA and were inhibited by their respective inhibitors, 7E3, SZ-1, aspirin and apyrase. Pretreatment of platelets with 7E3, SZ-1 or apyrase significantly inhibited TCIPA, while pretreatment with aspirin had no effect. Moreover, combined pretreatment of platelets with 7E3, SZ-1 and apyrase significantly inhibited TCIPA, compared to single inhibitors. Combinations of antiplatelet drugs may represent a promising strategy to prevent cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Lian

et al. 2012

Oncology Letters

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“…3b). The release of TxA 2 into the microenvironment activates TP receptors on platelets [442, 439, 60, 440, 443, 444]. Activation by Walker 256 carcinosarcoma cells, for example, induces arachidonic acid release followed by 12-lipoxygenase-mediated-conver-sion to 12(S)-HETE that further stimulates TCIPA [207].…”

Section: Eicosanoids and Tumor Cell-induced Platelet Aggregationmentioning

confidence: 99%

Platelets and cancer: a casual or causal relationship: revisited

Menter

Tucker

Kopetz

et al. 2014

Cancer Metastasis Rev

264

256

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Human platelets arise as subcellular fragments of megakaryocytes in bone marrow. The physiologic demand, presence of disease such as cancer, or drug effects can regulate the production circulating platelets. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. The most critical biological platelet response is serving as “First Responders” during the wounding process. The exposure of extracellular matrix proteins and intracellular components occurs after wounding. Numerous platelet receptors recognize matrix proteins that trigger platelet activation, adhesion, aggregation, and stabilization. Once activated, platelets change shape and degranulate to release growth factors and bioactive lipids into the blood stream. This cyclic process recruits and aggregates platelets along with thrombogenesis. This process facilitates wound closure or can recognize circulating pathologic bodies. Cancer cell entry into the blood stream triggers platelet-mediated recognition and is amplified by cell surface receptors, cellular products, extracellular factors, and immune cells. In some cases, these interactions suppress immune recognition and elimination of cancer cells or promote arrest at the endothelium, or entrapment in the microvasculature, and survival. This supports survival and spread of cancer cells and the establishment of secondary lesions to serve as important targets for prevention and therapy.

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“…Selective targeting of clotting intermediates in cancer may therefore be a novel therapeutic approach. BM-567, the mixed TXS inhibitor/receptor antagonist reduced tumor-cell induced platelet aggregation (TCIPA) in osteogenic sarcoma cells [192]. In colorectal cancer, observations of increased TXS [76] and TXB 2 [78] levels in cancer patients, relative to healthy controls, suggest that targeting this potent clotting intermediate may impact on colorectal cancer to restore anti-tumor reactivity.…”

Section: Pharmacological Agentsmentioning

confidence: 99%

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention

Cathcart

Lysaght

Pidgeon

2011

Cancer Metastasis Rev

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Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.

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Pharmacological evaluation of the novel thromboxane modulator BM-567 (II/II). Effects of BM-567 on osteogenic sarcoma-cell-induced platelet aggregation

Cited by 33 publications

References 12 publications

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs

Platelets and cancer: a casual or causal relationship: revisited

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention

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