Mitochondria in tumor cells studied by laser scanning confocal microscopy.
We present here a confocal fluorescence microscopy study of mitochondria in sensitive and resistant carcinoma cells by using two potentiometric probes of mitochondria, rhodamine 123 (R123) and dimethylaminostyryl-methylpyridiniumiodine. We have found that active mitochondria in sensitive MCF-7 and multidrug resistant MCF-7/DX carcinoma cells are very different in localization and morphology. In sensitive cells active mitochondria are found in the perinuclear region, whereas in the multidrug resistance (MDR) subline they are confined to the cell periphery. Interestingly, the MDR revertant verapamil has been found to restore in MCF-7/DX cells the same pattern of active mitochondria seen in sensitive cells. We have also studied R123 in human lung carcinoma A549 cells, which display a low responsivity to doxorubicin, and overexpress the lung resistance-related protein. In addition to perinuclear mitochondria, peripheral mitochondria with weaker fluorescence can be seen in this cell line. Interestingly, in the two examined carcinoma lines we have been able to recognize by image analysis a common new star-lobed morphology. Our results indicate that in resistant carcinoma cells two populations of mitochondria coexist with different localization, morphology, and activity.
Villa
Anna Maria
AM
INFM-UdR Milano Bicocca and Dipartimento di Biotecnologie e Bioscienze, Universita degli Studi di Milano Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Doglia
Silvia Maria
SM
D000230:Adenocarcinoma / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000503:physiopathology / Q000648:ultrastructure; D002277:Carcinoma / Q000503:physiopathology / Q000648:ultrastructure; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000648:ultrastructure; D018432:Drug Resistance, Multiple; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D008175:Lung Neoplasms / Q000648:ultrastructure; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000648:ultrastructure*; D009369:Neoplasms / Q000648:ultrastructure*; D010051:Ovarian Neoplasms / Q000648:ultrastructure; D011726:Pyridinium Compounds; D020112:Rhodamine 123
D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D020112:Rhodamine 123; C011786:2-(4-(dimethylamino)styryl)-1-methylpyridinium