Ticagrelor inhibits platelet-tumor cell interactions and metastasis in human and murine breast cancer.

We examined the potential of the reversible P2Y12 inhibitor ticagrelor, an agent used clinically to prevent cardiovascular and cerebrovascular events, to reduce tumor growth and metastasis. In vitro, MCF-7, MDA-MB-468, and MDA-MB-231 human mammary carcinoma cells exhibited decreased interaction with platelets treated with ticagrelor compared to untreated platelets. Prevention of tumor cell-platelet interactions through pretreatment of platelets with ticagrelor did not improve natural killer cell-mediated tumor cell killing of K562 myelogenous leukemia target cells. Additionally, ticagrelor had no effect on proliferation of 4T1 mouse mammary carcinoma cells co-cultured with platelets, or on primary 4T1 tumor growth. In an orthotopic 4T1 breast cancer model, ticagrelor (10 mg/kg), but not clopidogrel (10 mg/kg) or saline, resulted in reduced metastasis and improved survival. Ticagrelor treatment was associated with a marked reduction in tumor cell-platelet aggregates in the lungs at 10, 30 and 60 min post-intravenous inoculation. These findings suggest a role for P2Y12-mediated platelet activation in promoting metastasis, and provide support for the use of ticagrelor in the prevention of breast cancer spread. PMID: 29322294 [PubMed - as supplied by publisher]
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: Clin Exp Metastasis Source Type: research

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Publication date: Available online 7 July 2018Source: SteroidsAuthor(s): Nguyen Hoai Nam, Ninh Thi Ngoc, Tran Thi Hong Hanh, Nguyen Xuan Cuong, Nguyen Van Thanh, Do Thi Thao, Do Cong Thung, Phan Van Kiem, Chau Van MinhAbstractUsing various chromatographic separations, seventeen steroids including seven new compounds, verrucorosteroids A−F (1−6) and verrucorosterone (7), were isolated from the Vietnamese gorgonian Verrucella corona. Their structures were elucidated by spectroscopic analysis, including HR QTOF MS, 1D and 2D NMR. Among isolates, verrucorosterone (7), 5,6α-epoxy-3β-hydroxy-(22E)-ergosta-...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research
Publication date: 5 November 2018Source: Journal of Molecular Structure, Volume 1171Author(s): Renyer A. Costa, Earle Silva A. Junior, Guilherme Braule P. Lopes, Maria Lucia B. Pinheiro, Emmanoel V. Costa, Daniel P. Bezerra, Kelson OliveiraAbstractA theoretical and experimental DFT study of the vibrational, structural and quantum properties of annomontine (1) and N-hydroxyannomontine (2) alkaloids using the B3LYP exchange-correlation functional with 6-311G (2d, p) basis set is presented. The theoretical geometry optimization data of the two structures were compared with the X-ray data of (1) in the associated literature an...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
Publication date: Available online 7 July 2018Source: SteroidsAuthor(s): Nguyen Hoai Nam, Ninh Thi Ngoc, Tran Thi Hong Hanh, Nguyen Xuan Cuong, Nguyen Van Thanh, Do Thi Thao, Do Cong Thung, Phan Van Kiem, Chau Van MinhAbstractUsing various chromatographic separations, seventeen steroids including seven new compounds, verrucorosteroids A−F (1−6) and verrucorosterone (7), were isolated from the Vietnamese gorgonian Verrucella corona. Their structures were elucidated by spectroscopic analysis, including HR QTOF MS, 1D and 2D NMR. Among isolates, verrucorosterone (7), 5,6α-epoxy-3β-hydroxy-(22E)-ergosta-...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research
Publication date: 5 November 2018Source: Journal of Molecular Structure, Volume 1171Author(s): Renyer A. Costa, Earle Silva A. Junior, Guilherme Braule P. Lopes, Maria Lucia B. Pinheiro, Emmanoel V. Costa, Daniel P. Bezerra, Kelson OliveiraAbstractA theoretical and experimental DFT study of the vibrational, structural and quantum properties of annomontine (1) and N-hydroxyannomontine (2) alkaloids using the B3LYP exchange-correlation functional with 6-311G (2d, p) basis set is presented. The theoretical geometry optimization data of the two structures were compared with the X-ray data of (1) in the associated literature an...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research
Transcription factor MYB is essential for the tumorigenesis of multiple cancers, especially leukemia, breast cancer, colon cancer, adenoid cystic carcinoma and brain cancer. Thus, MYB has been regarded as an attractive target for tumor therapy. However, pioneer studies of antisense oligodeoxynucleotides against MYB, which were launched three decades ago in leukemia therapy, were discontinued because of their unsatisfactory clinical outcomes. In recent years, the roles of MYB in tumor transformation have become increasingly clear. Moreover, the regulatory mechanisms of MYB, such as the vital effects of MYB co-regulators on ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Cui Z, Li H, Liang F, Mu C, Mu Y, Zhang X, Liu J Abstract WD repeat domain 5 (WDR5) serves an important role in various biological functions through the epigenetic regulation of gene transcription. Aberrant expression of WDR5 has been observed in various types of human cancer, including prostate cancer, breast cancer and leukemia. However, the role of WDR5 expression and its clinical implications in hepatocellular carcinoma (HCC) remain largely unknown. The present study investigated the WDR5 expression pattern in HCC. It was demonstrated that the mRNA and protein levels of WDR5 were upregulated in HCC can...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Abstract Two new sphingofungins G (1) and H (2) with a five-membered lactone ring were identified from the solid-state fermentation of Aspergillus penicilliodes Speg., a dominant microorganism isolated previously from the post-fermentation of ripe Pu-er tea, together with six known metabolites. Their structures were elucidated by extensive spectroscopic methods. All of them were isolated from the mycelia culture of A. penicilliodes for the first time. The known compound, trypacidin, exhibited potent cytotoxities against five human cancer cell lines, e.g. myeloid leukemia HL-60, lung cancer A-549, hepatocellular ca...
Source: Natural Product Research - Category: Biochemistry Authors: Tags: Nat Prod Res Source Type: research
AbstractA series of quinazoline clubbed 1,3,5-triazine derivatives (QCT) were synthesized and evaluated for their in vitro anticancer activity against HeLa (human cervical cancer), MCF-7 (human breast cancer cell), HL-60 (human promyelocytic leukemia cell), HepG2 (human Hepatocellular carcinoma cell), and one normal cell line HFF (human foreskin fibroblasts). In vitro assay result encouraged to further move towards in ovo anticancer evaluation using chick embryo. The series of QCT derivatives showed higher anticancer and antiangiogenic activity against HeLa and MCF-7 cell lines. In the series, synthetic molecule8d,8l, and8...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: Life-span exposures to continuous and intermittent sinusoidal-50 Hz ELFEMFs, when administered alone, did not represent a significant risk factor for neoplastic development in our experimental rat model. In light of our previous results on the carcinogenic effects of ELFEMF in combination with formaldehyde and γ-radiation, further experiments are necessary to elucidate the possible role of ELFEMF as cancer enhancer in presence of other chemical and physical carcinogens. PMID: 29549848 [PubMed - as supplied by publisher]
Source: Environmental Research - Category: Environmental Health Authors: Tags: Environ Res Source Type: research
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