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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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DOI

10.1007/s10792-010-9383-y

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1432-0843

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HMBA induces cell death and potentiates doxorubici

Authors: Camilla Palumbo Loredana Albonici Roberto Bei Chiara Bocci Susanna Scarpa Paolo Di Nardo Andrea Modesti
Publish Date: 2004/06/26
Volume: 54, Issue: 5, Pages: 398-406
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Abstract

Malignant pleural mesothelioma MM a rare tumor characterized by high local invasiveness and low metastatic efficiency is poorly responsive to current therapeutic approaches The aim of the present study was to evaluate the cytotoxic efficacy of the hybrid polar compound hexamethylene bisacetamide HMBA either as a single agent or in combination with the anthracycline doxorubicin DOX against MM cellsThe MM cell lines MMB1 and MME1 were treated with HMBA DOX or with combinations of the two drugs Cell survival and death were assessed by the MTS assay and trypan blue staining/TUNEL respectively The interactions between drugs were evaluated by the method of Kern et al Western blot analysis was used to investigate the expression of Bcl2 family proteinsWhen administered alone HMBA dosedependently decreased the number of viable cells and increased the death rate of MMB1 and MME1 cultures Combinations of HMBA and DOX achieved a synergistic inhibition of MM cell survival and the simultaneous administration of HMBA counteracted the resistance induced by DOX in MME1 cells HMBA used at cytostatic concentrations reduced the ratio between antiapoptotic Bcl2 BclXL and proapoptotic Bax members of the Bcl2 family of proteins thus lowering the threshold for MM cell death commitment

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