Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve
Autor: | Aki Watanabe, Masaki Nakano, Sho Hosokawa, Toshiyuki Shudo, Akira Kakizuka, Yuma Sugiyama |
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Rok vydání: | 2019 |
Předmět: |
Cell type
Emodin uncoupler Melanoma Experimental Biology Cell Line Mice 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate In vivo Fallopia japonica melanoma Genetics Animals Glycolysis Protein Kinase Inhibitors Cell Proliferation 030304 developmental biology 0303 health sciences Plant Extracts Cell Biology Fibroblasts glycolytic reserve Warburg effect In vitro Mitochondria Cell biology chemistry Cancer cell Adenosine triphosphate Rhizome |
Zdroj: | Genes to Cells. 24:569-584 |
ISSN: | 1365-2443 1356-9597 |
Popis: | Many types of cancer cells show a characteristic increase in glycolysis, which is called the “Warburg effect.” By screening plant extracts, we identified one that decreases cellular adenosine triphosphate (ATP) levels and suppresses proliferation of malignant melanoma B16F10 cells, but not of noncancerous MEF cells. We showed that its active ingredient is emodin, which showed strong antiproliferative effects on B16F10 cells both in vitro and in vivo. Moreover, we also found that emodin can function as a mitochondrial uncoupler. Consistently, three known mitochondrial uncouplers also displayed potent antiproliferative effects and preferential cellular ATP reduction in B16F10 cells, but not in MEF cells. These uncouplers provoked comparable mitochondrial uncoupling in both cell types, but they manifested dramatically different cellular effects. Namely in MEF cells, these uncouplers induced three to fivefold increases in glycolysis from the basal state, and this compensatory activation appeared to be responsible for the maintenance of cellular ATP levels. In contrast, B16F10 cells treated with the uncouplers showed less than a twofold enhancement of glycolysis, which was not sufficient to compensate for the decrease of ATP production. Together, these results raise the possibility that uncouplers could be effective therapeutic agents specifically for cancer cells with prominent “Warburg effect.” |
Databáze: | OpenAIRE |
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