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Alterations of RNA Metabolism by Proteomic Analysis of Breast Cancer Cells Exposed to Marycin: A New Optically Active Porphyrin

[ Vol. 12 , Issue. 2 ]

Author(s):

Elena Taverna, Maida De Bortoli, Elisa Maffioli, Cristina Corno, Emilio Ciusani, Silvio Trivulzio, Arnaldo Pinelli, Gabriella Tedeschi, Paola Perego and Italia Bongarzone*   Pages 147 - 159 ( 13 )

Abstract:


Objective: Marycin is a porphyrin-type compound synthetically modified to spontaneously release fluorescence. This study is aimed at understanding possible mechanisms that could account for the antiproliferative effects observed in marycin. A proteomic approach was used to identify molecular effects. The proteome of proliferating MDA-MB-231 breast cancer cells was compared with that of marycin-treated cells.

Methods: Label-free proteomic analysis by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to reveal changes in protein expression and fluorescence microscopy and flow cytometry were used to detect subcellular organelle dysfunctions.

Results: The bioinformatic analysis indicated an enhancement of the expression of proteins remodeling RNA splicing and more in general, of RNA metabolism. Marycin did not localize into the mitochondria and did not produce a dramatic increase of ROS levels in MDA-MB-231 cells. Marycin stained organelles probably peroxisomes.

Conclusions: The results could support the possibility that the peroxisomes are involved in cell response to marycin.

Keywords:

Marycin, porphyrin, anti-proliferative effect, RNA metabolism, RNA splicing, peroxisomes, MDA-MB-231 breast cancer cells, LC-MS/MS.

Affiliation:

Molecular Mechanism Unit, Research Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Molecular Mechanism Unit, Research Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Center for Nano Science and Technology at Polimi, Istituto Italiano di Tecnologia, Fondazione Filarete, Milan, Center for Nano Science and Technology at Polimi, Istituto Italiano di Tecnologia, Fondazione Filarete, Milan, Laboratory of Clinical Pathology and Medical Genetics, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Laboratory of Clinical Pathology and Medical Genetics, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Dipartimento di Medicina Veterinaria (DiMeVet), University of Milan, Milan, Molecular Mechanism Unit, Research Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan

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