title: Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen.
abstract: Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet/anti-thrombotic agent.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Manasa K
authors.initials: MK
authors.lastname: Nayak
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Singh
authors.forename: Arnab
authors.initials: A
authors.lastname: Roy
authors.forename: Vivek
authors.initials: V
authors.lastname: Prakash
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D051379:Mice; D018715:Microscopy, Video; D010974:Platelet Aggregation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D011960:Receptors, Estrogen; D013629:Tamoxifen