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Therefore, the targeting of CSCs has potential for effective anticancer therapies. Curcumin is one of the most widely characterized phytochemicals with tumor\u2010suppressive potential. GO\u2010Y030 is a novel curcumin analogue exhibiting a much stronger growth\u2010inhibitory effect than curcumin. In the present study, we verified the potency of GO\u2010Y030 against a CSC population. We observed that GO\u2010Y030 suppressed CSC sphere\u2010forming ability in several cancer cell lines. Interestingly, a specific inhibitor of heat shock protein (HSP) 70 also exhibited effects similar to GO\u2010Y030 (i.e. inhibition of CSC sphere formation and upregulation of HSP70 and HSP40 protein expression), suggesting that HSP70 and\/or HSP40 might be target molecules of GO\u2010Y030. We then performed an <jats:italic>in\u2009vitro<\/jats:italic> HSP70\/HSP40\u2010mediated refolding activity assay and observed that chaperone activity was efficiently inhibited by GO\u2010Y030. Finally, we performed a substrate\u2010binding assay to show that GO\u2010Y030 reduced the binding of both HSP70 and HSP40 with their substrates. HSPs prevent denaturation or unfolding of client proteins under stressful conditions such as high temperature. Because CSCs by nature adapt to various stresses by reinforcing protein\u2010folding activity, the function of HSP70\/HSP40 is important for the maintenance of CSC population. Our data suggest that GO\u2010Y030 may impair stress tolerance in CSCs by inhibiting the interaction of HSP70\/HSP40 with their substrate proteins and disrupting the function of HSP70\/HSP40, thereby contributing to a reduction of the CSC population.<\/jats:p>","DOI":"10.1002\/2211-5463.13550","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T12:39:08Z","timestamp":1673959148000},"page":"434-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A curcumin analogue <scp>GO\u2010Y030<\/scp> depletes cancer stem cells by inhibiting the interaction between the <scp>HSP70<\/scp>\/<scp>HSP40<\/scp> complex and its substrates"],"prefix":"10.1002","volume":"13","author":[{"given":"Maya","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Molecular and Tumour Pathology Akita University Graduate School of Medicine  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