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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.
Highlights
Cancer remains one of the most common causes of death worldwide
Cancer cells exhibit a stronger mitochondrial membrane potential, a particular feature that opens the way to control of cell proliferation and survival by means of regulation of the mechanical properties of mitochondrial membranes
This strong membrane potential of mitochondria allows the accumulation of cationic lipophilic molecules within the mitochondrial matrix at non-effective concentrations of normal cells
Summary
Cancer remains one of the most common causes of death worldwide. Lung cancer is usually detected at later stages of development [1]. Traditional chemotherapeutics interfere with replication or cell division to prevent cell growth, increase cell death and restrict the spreading of the cancer [4]. Side effects of traditional cancer treatments as surgery, chemotherapy or radiation therapy are significant as many healthy cells are killed during the treatment, due to the lack of target specificity. With the aim to target only cancer cells, a new generation of cancer treatment has been developed recently known as the targeted cancer therapy [5], where pharmacological agents
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