A novel quinone-based derivative (DTNQ-Pro) induces apoptotic death via modulation of heat shock protein expression in Caco-2 cells |
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Authors: | Isabel Gomez-Monterrey Pietro Campiglia Alessia Bertamino Claudio Aquino Marina Sala Paolo Grieco Alessandra Dicitore Daniela Vanacore Amalia Porta Bruno Maresca Ettore Novellino Paola Stiuso |
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Affiliation: | 1Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy;2Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Salerno, Italy;3Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy |
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Abstract: | Background and purpose:The resistance of human colon adenocarcinoma cells to antineoplastic agents may be related to the high endogenous expression of stress proteins, including the family of heat shock proteins (HSPs). Recently, a quinone-based pentacyclic derivative, DTNQ-Pro, showed high cytotoxic activity in human colon carcinoma cell lines. The aim of the present study was to determine the precise cellular mechanisms of this cytotoxic action of DTNQ-Pro.Experimental approach:Using human colorectal carcinoma-derived Caco-2 cells as a model, we studied the effects of DTNQ-Pro on cellular viability and oxidative stress; HSP70 and HSP27 accumulation; and cell cycle, differentiation and apoptosis.Key results:Incubation of Caco-2 cells with DTNQ-Pro reduced cell growth and increased the levels of reactive oxygen species in mitochondria. After 48 h of treatment, cells surviving showed an increased expression of Mn-superoxide dismutase (SOD), nitric oxide production and membrane lipid peroxidation. Treatment with DTNQ-Pro decreased HSP70 expression, and redistributed HSP27 and vimentin within the cell. DTNQ-Pro down-regulated the expression of A and B cyclins with arrest of the cell cycle in S phase and increased cellular differentiation. A second treatment of Caco-2 cells with DTNQ-Pro induced cellular death by activation of the apoptotic pathway.Conclusions and implications:DTNQ-Pro causes Caco-2 cell death by induction of apoptosis via inhibition of HSP70 accumulation and the intracellular redistribution of HSP27. These findings suggest the potential use of DTNQ-Pro in combination chemotherapy for colon cancer. |
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Keywords: | cellular differentiation apoptosis Caco-2 cell line heat shock proteins quinone-based anti-tumour agents |
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