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Enhanced Cytotoxic Activity of Mitochondrial Mechanical Effectors in Human Lung Carcinoma H520 Cells: Pharmaceutical Implications for Cancer Therapy

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González Rubio, Sergio and Montero Pastor, Nuria and García, Carolina and Almendro Vedia, Víctor G. and Ferrer, Irene and Natale, Paolo and Paz-Ares, Luis and Lillo, M. Pilar and López-Montero, Iván (2018) Enhanced Cytotoxic Activity of Mitochondrial Mechanical Effectors in Human Lung Carcinoma H520 Cells: Pharmaceutical Implications for Cancer Therapy. Frontiers in Oncology, 8 . ISSN 2234-943X

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Official URL: https://doi.org/10.3389/fonc.2018.00514



Abstract

Cancer cell mitochondria represent an attractive target for oncological treatment as they have unique hallmarks that differ from their healthy counterparts, as the presence of a stronger membrane potential that can be exploited to specifically accumulate cytotoxic cationic molecules. Here, we explore the selective cytotoxic effect of 10-N-nonyl acridine orange (NAO) on human lung carcinoma H520 cells and compare them with healthy human lung primary fibroblasts. NAO is a lipophilic and positively charged molecule that promotes mitochondrial membrane adhesion that eventually leads to apoptosis when incubated at high micromolar concentration. We found an enhanced cytotoxicity of NAO in H520 cancer cells. By means Fluorescence lifetime imaging microscopy (FLIM) we also confirmed the formation of H-dimeric aggregates originating from opposing adjacent membranes that interfere with the mitochondrial membrane structure. Based on our results, we suggest the mitochondrial membrane as a potential target in cancer therapy to mechanically control the cell proliferation of cancer cells.


Item Type:Article
Additional Information:

The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (ERC grant agreement n° 338133)

Uncontrolled Keywords:NAO, mitochondrial targeting, membrane adhesion, cancer therapy, NSCLC cells, FLIM, phasor analysis
Subjects:Medical sciences > Medicine > Oncology
Medical sciences > Biology > Cytology
Medical sciences > Biology > Biotechnology
ID Code:60121
Deposited On:22 Apr 2020 18:07
Last Modified:22 Apr 2020 18:07

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