Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve. (28th July 2019)

• Record Type: Journal Article
• Authors: Sugiyama, Yuma; Shudo, Toshiyuki; Hosokawa, Sho; Watanabe, Aki; Nakano, Masaki; Kakizuka, Akira
• Is Part Of: Genes to cells. Volume 24:Number 8(2019)
• Page Start: 569
• Page End: 584
• Publication Date: 2019-07-28
• Subjects: adenosine triphosphate -- emodin -- glycolytic reserve -- melanoma -- uncoupler; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12712
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: 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." Abstract : Mitochondrial uncouplers, for example, emodin, produce strong antiproliferative effects on malignant melanoma B16F10 cells, which are cancer cells with a prominent "Warburg effect" or poor glycolytic reserve.