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Open AccessArticle

3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells

1
Department of Biomedical and Clinical Sciences “Luigi Sacco”, Università degli Studi di Milano, 20157 Milano, Italy
2
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
3
Unit of Clinical Pharmacology, “Luigi Sacco” University Hospital, ASST Fatebenefratelli Sacco, 20157 Milan, Italy
4
ALBA Synchrotron Light Facility, Carrer de la Llum 2-26, 08290 Cerdanyola del Vallès, Spain
5
Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy
6
National Institute of Biostructures and Biosystems, 00136 Roma, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Cancers 2019, 11(9), 1254; https://doi.org/10.3390/cancers11091254
Received: 26 July 2019 / Revised: 23 August 2019 / Accepted: 23 August 2019 / Published: 27 August 2019
(This article belongs to the Special Issue Mitochondria and Cancer)
Drug resistance remains a major obstacle in cancer treatment. Because mitochondria mediate metabolic reprogramming in cancer drug resistance, we focused on these organelles in doxorubicin sensitive and resistant colon carcinoma cells. We employed soft X-ray cryo nano-tomography to map three-dimensionally these cells at nanometer-resolution and investigate the correlation between mitochondrial morphology and drug resistance phenotype. We have identified significant structural differences in the morphology of mitochondria in the two strains of cancer cells, as well as lower amounts of Reactive oxygen species (ROS) in resistant than in sensitive cells. We speculate that these features could elicit an impaired mitochondrial communication in resistant cells, thus preventing the formation of the interconnected mitochondrial network as clearly detected in the sensitive cells. In fact, the qualitative and quantitative three-dimensional assessment of the mitochondrial morphology highlights a different structural organization in resistant cells, which reflects a metabolic cellular adaptation functional to survive to the offense exerted by the antineoplastic treatment. View Full-Text
Keywords: mitochondria; multidrug resistance; doxorubicin; cellular metabolism; nanoscale imaging; soft X-ray cryo tomography; transmission electron microscopy mitochondria; multidrug resistance; doxorubicin; cellular metabolism; nanoscale imaging; soft X-ray cryo tomography; transmission electron microscopy
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MDPI and ACS Style

Moscheni, C.; Malucelli, E.; Castiglioni, S.; Procopio, A.; De Palma, C.; Sorrentino, A.; Sartori, P.; Locatelli, L.; Pereiro, E.; Maier, J.A.; Iotti, S. 3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells. Cancers 2019, 11, 1254. https://doi.org/10.3390/cancers11091254

AMA Style

Moscheni C, Malucelli E, Castiglioni S, Procopio A, De Palma C, Sorrentino A, Sartori P, Locatelli L, Pereiro E, Maier JA, Iotti S. 3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells. Cancers. 2019; 11(9):1254. https://doi.org/10.3390/cancers11091254

Chicago/Turabian Style

Moscheni, Claudia; Malucelli, Emil; Castiglioni, Sara; Procopio, Alessandra; De Palma, Clara; Sorrentino, Andrea; Sartori, Patrizia; Locatelli, Laura; Pereiro, Eva; Maier, Jeanette A.; Iotti, Stefano. 2019. "3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells" Cancers 11, no. 9: 1254. https://doi.org/10.3390/cancers11091254

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