The hallmark of ovarian cancer is its high mortality rate attributed to the existence of cancer stem cells (CSCs) subpopulations which result in therapy recurrence and metastasis. A series of C-29-substituted and/or different A/B ring of celastrol derivatives were synthesized and displayed potential inhibition against ovarian cancer cells SKOV3, A2780 and OVCAR3. Among them, compound 6c exhibited the most potent anti-proliferative activity and selectivity, gave superior anti-CSC effects through inhibition of the sphere formation and downregulation of the percentage of CD44+CD24- and ALDH+ cells. Further mechanism research demonstrated that compound 6c could attenuate the expression of STAT3 and p-STAT3. The results suggested that the inhibition of celastrol derivative 6c on ovarian cancer cells may be related to resistance to cancer stem-like characters and regulation of STAT3 pathway.
Keywords: Cancer stem cell; Celastrol derivatives; Ovarian cancer; STAT3.
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