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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

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

Author(s): Elena Taverna, Maida De Bortoli, Elisa Maffioli, Cristina Corno, Emilio Ciusani, Silvio Trivulzio, Arnaldo Pinelli, Gabriella Tedeschi, Paola Perego and Italia Bongarzone*

Volume 12, Issue 2, 2019

Page: [147 - 159] Pages: 13

DOI: 10.2174/1874467212666190204102112

Price: $65

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.

Graphical Abstract

[1]
Josefsen, L.B.; Boyle, R.W. Photodynamic therapy and the development of metal-based photosensitisers. Met. Based Drugs, 2008, 2008, 276109.
[2]
Dolmans, D.E.; Fukumura, D.; Jain, R.K. Photodynamic therapy for cancer. Nat. Rev. Cancer, 2003, 3, 380-387.
[3]
Huang, H.; Song, W.; Rieffel, J.; Lovell, J.F. Emerging applications of porphyrins in photomedicine. Front. Phys., 2015, 3
[http://dx.doi.org/10.3389/fphy.2015.00023]
[4]
Pinelli, A.; Trivulzio, S.; Von Hoff, D.D.; Monti, D.; Manitto, P. Observations on the chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative. Cancer Lett., 1988, 38, 257-269.
[5]
Perego, P.; Romanelli, S.; Carenini, N.; Magnani, I.; Leone, R.; Bonetti, A.; Paolicchi, A.; Zunino, F. Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to Taxol. Ann. Oncol., 1998, 9, 423-430.
[6]
Zarini, E.; Supino, R.; Pratesi, G.; Laccabue, D.; Tortoreto, M.; Scanziani, E.; Ghisleni, G.; Paltrinieri, S.; Tunesi, G.; Nava, M. Biocompatibility and tissue interactions of a new filler material for medical use. Plast. Reconstr. Surg., 2004, 114, 934-942.
[7]
Bozzi, F.; Mogavero, A.; Varinelli, L.; Belfiore, A.; Manenti, G.; Caccia, C.; Volpi, C.C.; Beznoussenko, G.V.; Milione, M.; Leoni, V.; Gloghini, A.; Mironov, A.A.; Leo, E.; Pilotti, S.; Pierotti, M.A.; Bongarzone, I.; Gariboldi, M. MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. J. Exp. Clin. Cancer Res., 2017, 36, 16.
[8]
Darzynkiewicz, Z.; Staiano-Coico, L.; Melamed, M.R. Increased mitochondrial uptake of rhodamine 123 during lymphocyte stimulation. Proc. Natl. Acad. Sci. USA, 1981, 78, 2383-2387.
[9]
Lizard, G.; Chardonnet, Y.; Chignol, M.C.; Thivolet, J. Evaluation of mitochondrial content and activity with nonyl-acridine orange and rhodamine 123: Flow cytometric analysis and comparison with quantitative morphometry. Comparative analysis by flow cytometry and quantitative morphometry of mitochondrial content and activity. Cytotechnology, 1990, 3, 179-188.
[10]
Iwagaki, H.; Fuchimoto, S.; Miyake, M.; Oirta, K. Increased mitochondrial uptake of rhodamine 123 during interferon-gamma stimulation in Molt 16 cells. Lymphokine Res., 1990, 9, 365-369.
[11]
Iametti, B.S.; Tedeschi, G.; Oungre, E.; Bonomi, F. Primary structure of kappa-casein isolated from mares’ milk. J. Dairy Res., 2001, 68, 53-61.
[12]
Coccetti, P.; Tripodi, F.; Tedeschi, G.; Nonnis, S.; Marin, O.; Fantinato, S.; Cirulli, C.; Vanoni, M.; Alberghina, L. The CK2 phosphorylation of catalytic domain of Cdc34 modulates its activity at the G1 to S transition in Saccharomyces cerevisiae. Cell Cycle, 2008, 7, 1391-1401.
[13]
Cox, J.; Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol., 2008, 26, 1367-1372.
[14]
Zanotti, L.; Angioni, R.; Cali, B.; Soldani, C.; Ploia, C.; Moalli, F.; Gargesha, M.; D’Amico, G.; Elliman, S.; Tedeschi, G.; Maffioli, E.; Negri, A.; Zacchigna, S.; Sarukhan, A.; Stein, J.V.; Viola, A. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1. Leukemia, 2016, 30, 1143-1154.
[15]
Vizcaino, J.A.; Csordas, A.; del-Toro, N.; Dianes, J.A.; Griss, J.; Lavidas, I.; Mayer, G.; Perez-Riverol, Y.; Reisinger, F.; Ternent, T.; Xu, Q.W.; Wang, R.; Hermjakob, H. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res., 2016, 44, D447-D456.
[16]
Wang, J.; Vasaikar, S.; Shi, Z.; Greer, M.; Zhang, B. WebGestalt 2017: A more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res., 2017, 45, W130-W137.
[17]
Mi, H.; Muruganujan, A.; Casagrande, J.T.; Thomas, P.D. Large-scale gene function analysis with the PANTHER classification system. Nat. Protoc., 2013, 8, 1551-1566.
[18]
Park, S.G.; Schimmel, P.; Kim, S. Aminoacyl tRNA synthetases and their connections to disease. Proc. Natl. Acad. Sci. USA, 2008, 105, 11043-11049.
[19]
Guo, M.; Schimmel, P. Essential nontranslational functions of tRNA synthetases. Nat. Chem. Biol., 2013, 9, 145-153.
[20]
Kim, Y.W.; Kwon, C.; Liu, J.L.; Kim, S.H.; Kim, S. Cancer association study of aminoacyl-tRNA synthetase signaling network in glioblastoma. PLoS One, 2012, 7, e4096.
[21]
Montecucco, A.; Biamonti, G. Pre-mRNA processing factors meet the DNA damage response. Front. Genet., 2013, 4, 102.
[22]
Bargou, R.C.; Jurchott, K.; Wagener, C.; Bergmann, S.; Metzner, S.; Bommert, K.; Mapara, M.Y.; Winzer, K.J.; Dietel, M.; Dorken, B.; Royer, H.D. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat. Med., 1997, 3, 447-450.
[23]
Ma, C.; Agrawal, G.; Subramani, S. Peroxisome assembly: matrix and membrane protein biogenesis. J. Cell Biol., 2011, 193, 7-16.
[24]
Angela, M.; Endo, Y.; Asou, H.K.; Yamamoto, T.; Tumes, D.J.; Tokuyama, H.; Yokote, K.; Nakayama, T. Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARgamma directs early activation of T cells. Nat. Commun., 2016, 7, 13683.
[25]
Chi, C.; Du, Y.; Ye, J.; Kou, D.; Qiu, J.; Wang, J.; Tian, J.; Chen, X. Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology. Theranostics, 2014, 4, 1072-1084.

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