Abstract
Methods of fluorescence spectroscopy and microscopy—including intensity and lifetime (FLIM) images—are used to examine uptake, intracellular location and interaction of the chemotherapeutic drug doxorubicin in MCF-7 human breast cancer cells as a function of cholesterol content. By comparing cells with natural and decreased cholesterol levels after 2 h or 24 h incubation with doxorubicin, we observed that higher fluorescence intensities and possibly shortened fluorescence lifetimes—reflecting increased uptake of the drug and more pronounced drug response—are concomitant with higher membrane fluidity.
Highlights
IntroductionDoxorubicin, an anthracycline antibiotic, is used as a cytostatic drug in cancer chemotherapy, such as breast cancer, bronchial carcinoma and lymphoma, and has been studied for several decades [1,2]
Doxorubicin, an anthracycline antibiotic, is used as a cytostatic drug in cancer chemotherapy, such as breast cancer, bronchial carcinoma and lymphoma, and has been studied for several decades [1,2].The drug is taken up by cells due to passive diffusion through their membrane and intercalates in DNA strands, where it causes chromatin condensation and initiates apoptosis [3]
Intensity of Doxorubicin Fluorescence Increases after Cholesterol Depletion
Summary
Doxorubicin, an anthracycline antibiotic, is used as a cytostatic drug in cancer chemotherapy, such as breast cancer, bronchial carcinoma and lymphoma, and has been studied for several decades [1,2]. The drug is taken up by cells due to passive diffusion through their membrane and intercalates in DNA strands, where it causes chromatin condensation and initiates apoptosis [3]. Due to its fluorescence properties [4] doxorubicin can be localized within the cells, e.g., by wide-field microscopy, and, fluorescence lifetime measurements [5,6,7,8] permit assessing. 2013, 14 intermolecular interactions with its microenvironment. Low or moderate light doses are needed to avoid phototoxic effects in microscopic experiments [9]
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