Niclosamide suppresses macrophage-induced inflammation in endometriosis†

Abstract

Endometriosis is a common gynecological disease, which causes chronic pelvic pain and infertility in women of reproductive age. Due to limited efficacy of current treatment options, a critical need exists to develop new and effective treatments for endometriosis. Niclosamide is an efficacious and FDA-approved drug for the treatment of helminthosis in humans that has been used for decades. We have reported that niclosamide reduces growth and progression of endometriosis-like lesions via targeting STAT3 and NFĸB signaling in a mouse model of endometriosis. To examine the effects of niclosamide on macrophage-induced inflammation in endometriosis, a total of 29 stage III–IV endometrioma samples were used to isolate human endometriotic stromal cells (hESCs). M1 or M2 macrophages were isolated and differentiated from fresh human peripheral blood samples. Then, hESCs were cultured in conditioned media (CM) from macrophages with/without niclosamide. Niclosamide dose dependently reduced cell viability and the activity of STAT3 and NFκB signaling in hESCs. While macrophage CM stimulated cell viability in hESCs, niclosamide inhibited this stimulation. Macrophage CM stimulated the secretion of proinflammatory cytokines and chemokines from hESCs. Most of these secreted factors were inhibited by niclosamide. These results indicate that niclosamide is able to reduce macrophage-induced cell viability and cytokine/chemokine secretion in hESCs by inhibiting inflammatory mechanisms via STAT3 and/or NFκB signaling.

Expression of BDNF and TrKB in Endometriosis and Dysmenorrhea

“…Binding BDNF to TrKB, or activating PI3K pathway can inhibit proapoptotic protein activation and activate antiapoptotic protein Bcl-2 (9); or activating MAPK signaling pathway can in uence transcription factor and activate Bcl-2 (10); co-inhibit shedding endometrium from anoikis. Our study found that there was a signi cant difference in the expression of BDNF and TrKB between endometriosis endometrium and non-endometriosis endometrium, which is consistent with literature reported (11,12). Moreover, this study showed that the expression of BDNF and TrKB in ovarian endometriotic lesions was higher than that in eutopic endometrium, which is similar to Borghese et al who found that the expression of BDNF in ovarian endometriotic lesions was higher than that in eutopic endometrium.…”

Efficacy of niclosamide on the intra‐abdominal inflammatory environment in endometriosis

“…We have recently determined that a small molecule, niclosamide, could be a potential new effective therapy for endometriosis. [27][28][29] Our recent findings have demonstrated that niclosamide reduces the growth and progression of endometriosis-like lesions (ELL) and inhibits inflammatory signaling such as STAT3 and NFκB in the ELL in a mouse model of induced endometriosis. 27 RNA-sequencing analysis has shown that transcripts associated with inflammatory responses were reduced by niclosamide.…”

Application of Anti-Inflammatory Agents in Prostate Cancer

“…Therefore, it potentially has broad clinical applications for the treatment of diseases other than those caused by parasites, including metabolic diseases, infection, and cancer [ 254 ]. Niclosamide suppresses macrophage-induced inflammation via STAT3 and/or NF-κB signaling [ 255 ]. In addition, niclosamide was identified as a potent androgen receptor splice variant 7 (AR-V7) inhibitor in prostate cancer cells [ 256 ].…”