Auranofin, an antirheumatic drug, shows anticancer stem cell potential via suppression of the Stat3 signal
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Accumulating data have shown that targeting breast cancerstem cells (CSCs) is an auspicious way for anticancer therapies. This study demonstrated that the antirheumatic drug auranofinis a potent CSC inhibitor with anti-CSC action on breastcancer. This research focused on investigating the effect ofauranofin on breast cancer and CSCs and its cellular mechanism. Mammosphere formation, colony formation, levels ofCD44high/CD24low, and aldehyde dehydrogenase 1 expression inthe cells were evaluated after auranofin treatment. Theanti-CSC properties of auranofin were further examined by gelshift assay and cytokine detection. Auranofin suppressed cellgrowth, colony formation, migration, and mammosphere formationand triggered apoptosis in breast cancer. Auranofindecreased the CD44high/CD24low- and aldehyde dehydrogenaseexpressedsubpopulations, as well as the Stat3-DNA interactionand phosphorylated Stat3 level. Auranofin also decreasedthe extracellular levels of interleukin-8 (IL-8) in the mammospheremedia. Auranofin suppressed the Stat3/IL-8 signal andkilled CSCs; therefore, it may be a potential target for CSCs.
Abstract
Accumulating data have shown that targeting breast cancerstem cells (CSCs) is an auspicious way for anticancer therapies. This study demonstrated that the antirheumatic drug auranofinis a potent CSC inhibitor with anti-CSC action on breastcancer. This research focused on investigating the effect ofauranofin on breast cancer and CSCs and its cellular mechanism. Mammosphere formation, colony formation, levels ofCD44high/CD24low, and aldehyde dehydrogenase 1 expression inthe cells were evaluated after auranofin treatment. Theanti-CSC properties of auranofin were further examined by gelshift assay and cytokine detection. Auranofin suppressed cellgrowth, colony formation, migration, and mammosphere formationand triggered apoptosis in breast cancer. Auranofindecreased the CD44high/CD24low- and aldehyde dehydrogenaseexpressedsubpopulations, as well as the Stat3-DNA interactionand phosphorylated Stat3 level. Auranofin also decreasedthe extracellular levels of interleukin-8 (IL-8) in the mammospheremedia. Auranofin suppressed the Stat3/IL-8 signal andkilled CSCs; therefore, it may be a potential target for CSCs.