Mitochondria in cardiac muscle cells and myoblast-fused myotubes display unusually long (3-5 days) retention times of rhodamine 123, a mitochondria-specific fluorescent probe, in living cells. Among 50 keratin-positive carcinoma or transformed epithelial cell lines tested, mitochondria with prolonged rhodamine 123 retention are detected in most of the transitional cell carcinoma, adenocarcinoma, and chemical carcinogen-transformed epithelial cell lines and in some squamous cell carcinoma lines but notin any oat cell carcinoma lines. The presence of mitochondria having unusual dye retention may be useful for diagnosis and exploitable for chemotherapy of certain human carcinomas.
Carcinoma cells and normal epithelial cells differ in the mitochondrial retention of a permeant cationic compound, rhodamine 123. The possibility of utilizing this difference in carcinoma chemotherapy was investigated. Rhodamine 123 exhibited anticarcinoma activity in mice, and this activity was potentiated by 2-deoxyglucose.
Rhodamine-123, a cationic laser dye, markedly reduced the clonal growth of carcinoma cells but had little effect on nontumorigenic epithelial cells in vitro. This selective inhibitory effect of Rhodamine-123 on some carcinomas is unusual since known anticancer drugs, such as arabinosyl cytosine and methotrexate, have not been shown to exhibit such selectivity in vitro.
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