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Role of heme oxygenase-1 and its reaction product, carbon monoxide, in manifestation of breast cancer stem cell-like properties: Notch-1 as a putative target

Cited 19 time in Web of Science Cited 21 time in Scopus

Kim, Do-Hee; Yoon, Hyo-Jin; Cha, Young-Nam; Surh, Young-Joon

Issue Date
Taylor & Francis
Free Radical Research, Vol.52 No.11-12, pp.1336-1347
Cancer stem cells (CSCs) constitute a subpopulation of transformed cells that possess intrinsic ability to undergo selfrenewal and differentiation, which drive tumour resistance and cancer recurrence. It has been reported that CSCs possess enhanced protection against oxidative stress induced by reactive oxygen species compared with nonstem-like cancer cells. In the present work, we investigated the role of heme oxygenase-1 (HO-1), a representative antioxidant enzyme, on the stemness and selfrenewal of human breast CSCs. We found that pharmacologic or genetic inhibition of HO-1 attenuated the sphere formation, whereas HO-1 inducers enhanced the number and the size of tumourspheres in breast CSCs. Carbon monoxide (CO) is endogenously generated as a consequence of degradation of heme by HO-1. The proportion of populations of CD44(+)/CD24(-) cells retaining CSC properties was increased in MDA-MB-231 cells treated with a CO-releasing molecule (CORM-2). Following CORM-2 treatment, the expression of Notch-1 and related genes Jagged-1 and Hes1 was increased, which was accompanied by the mammosphere formation. Taken together, these findings suggest that HO-1-derived CO production stimulates the formation of mammospheres in breast cancer cells through activation of Notch-1 signalling.
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  • College of Pharmacy
  • Department of Pharmacy
Research Area Agricultural Sciences


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