title: Carmustine induces platelet apoptosis.
abstract: Carmustine is one of the alkylating chemotherapeutic agents, which are used to treat various types of cancers, such as brain tumors, Hodgkins and non-Hodgkins lymphoma and multiple myeloma. However, carmustine has the side effect of thrombocytopenia, and the mechanism is not completely understood. In this study, we show that carmustine dose-dependently induced depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax, down-regulation of Bcl-2 and caspase-3 activation. Carmustine did not induce surface expression of P-selectin or PAC-1 binding, whereas, obviously reduced collagen and thrombin-induced platelet aggregation. Dicumarol, c-Jun NH2-terminal kinase-specific inhibitor, reduced carmustine-induced ΔΨm depolarization in platelets. The numbers of circulating platelets were reduced, and the tail bleeding time was significantly increased in mice that were injected with carmustine. Taken together, these data indicate that carmustine induced platelet apoptosis, suggesting the possible pathogenesis of thrombocytopenia in patients treated with carmustine.
authors: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health , Suzhou , China.
authors: Jie
authors: J
authors: Zhang
authors: Mengxing
authors: M
authors: Chen
authors: Yiwen
authors: Y
authors: Zhang
authors: Lili
authors: L
authors: Zhao
authors: Rong
authors: R
authors: Yan
authors: Kesheng
authors: K
authors: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002330:Carmustine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D023421:Models, Animal; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases; D013917:Thrombin; D053148:Caspase 3; D002330:Carmustine
keywords: Apoptosis; carmustine; platelets; thrombocytopenia