Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells.

摘要: // Maria Lucibello 1 , Sara Adanti Ester Antelmi 2 Dario Dezi Stefania Ciafre Luisa Carcangiu Manuela Zonfrillo Giuseppe Nicotera Lorenzo Sica Filippo De Braud Pasquale Pierimarchi Institute of Translational Pharmacology, National Research Council, Rome, Italy Medical Oncology Department, Pathology and Molecular Biology Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Correspondence to: Lucibello, e-mail: maria.lucibello@ift.cnr.it Keywords: Advanced breast cancer, phospho-TCTP, DHA, target therapy, combination therapy Received: September 22, 2014      Accepted: December 16, Published: March 12, 2015 ABSTRACT Upregulation Translationally Controlled Tumor Protein (TCTP) is associated with poorly differentiated aggressive tumors, including but the underlying mechanism(s) are still debated. Here, we show that in cancer cell lines TCTP primarily localized nucleus, mostly phosphorylated form. The effects Dihydroartemisinin (DHA), an anti-malaria agent binds TCTP, were tested on cells. DHA decreases proliferation induces apoptotic death by targeting form TCTP. Remarkably, enhances anti-tumor Doxorubicin triple negative cells resulting increased level apoptosis. also synergizes Trastuzumab, used to treat HER2/neu positive cancers, induce apoptosis tumor Finally, present new clinical data nuclear phospho-TCTP overexpression primary tissue high histological grade, increase expression Ki-67 ER-negative subtypes. Notably, levels trastuzumab-resistant suggesting a possible role as prognostic marker. In conclusion, effect vitro conventional chemotherapeutics suggests novel therapeutic strategy identifies promising for advanced cancer.