title: JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin.
abstract: Recent evidence shows that tumor microenvironment containing heterogeneous cells may be involved in cancer initiation, growth and tumor cell response to anticancer therapy. Chemotherapy was designed to make toxic impact on malicious cells in organisms, however, the means to protect healthy cells against chemical toxicity are still unsuccessful. As known, the majority of tumor surrounding cells are cancer-associated adipocytes which influence cancer development, progression and treatment. Targeting the components of tumor microenvironment in combination with conventional cancer treatment may become an effective cancer therapy strategy. However, little is known about adipocyte death mechanisms during combined chemo- and targeted therapy. The importance of c-Jun-NH<inf>2</inf>-terminal kinase (JNK) signaling in tumor development and treatment has been demonstrated using various in vitro and in vivo cancer models. The aim of this study was to ascertain adipocyte viability during simultaneous stress kinase JNK inhibition and exposure to one of the most commonly used anticancer drugs cis-diamminedichloroplatinum II (cisplatin). Our model involved adipocyte-like cells (ADC) which were obtained during in vitro differentiation of adult rabbit muscle-derived stem cells. Cisplatin induced apoptotic cell death. During 24-hr cisplatin treatment gradual, strong and prolonged increase of both JNK and its target protein c-Jun phosphorylation was found in ADC. Pre-treatment of cells with SP600125 decreased cisplatin-induced activation of c-Jun and promoted apoptosis. Upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-2 proteins were found to be regulated in JNK-dependent manner. Thus, the results prove the antiapoptotic role of activated JNK in adipocyte-like cells treated with cisplatin.
authors.affiliation: Vilnius University Institute of Biochemistry, Department of Molecular Cell Biology, Lithuania.
authors.forename: Natalija
authors.initials: N
authors.lastname: Krestnikova
authors.forename: Aurimas
authors.initials: A
authors.lastname: Stulpinas
authors.forename: Ausra
authors.initials: A
authors.lastname: Imbrasaite
authors.forename: Goda
authors.initials: G
authors.lastname: Sinkeviciute
authors.forename: Audrone Valerija
authors.initials: AV
authors.lastname: Kalvelyte
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009132:Muscles / Q000166:cytology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011817:Rabbits; D013234:Stem Cells / Q000187:drug effects*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; D002945:Cisplatin