Discovery of semisynthetic celastrol derivatives exhibiting potent anti-ovarian cancer stem cell activity and STAT3 inhibition

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.

Automated summary

Ovarian cancer is characterized by its high mortality rate due to the presence of cancer stem cells, which lead to treatment recurrence and metastasis. A study found that the celastrol derivative 6c showed potential inhibition against ovarian cancer cells and exhibited anti-cancer stem cell effects by inhibiting sphere formation and regulating cell surface markers. Furthermore, compound 6c also attenuated the expression of the STAT3 pathway, suggesting its role in inhibiting ovarian cancer cells.