Curcumol Attenuates Endometriosis by Inhibiting the JAK2/STAT3 Signaling Pathway

• Published in: Medical science monitor Vol. 28; p. e934914
• Main Authors: Wang, Yan, Nie, Xiao-Bo, Liu, Su-Jun, Liu, Jiao, Bian, Wen-Hui
• Format: Journal Article
• Language: English
• Published: United States International Scientific Literature, Inc 13.03.2022
• Subjects: Adult; Apoptosis; Cell Proliferation; Cell Survival; Clinical Research; DNA - genetics; Drugs, Chinese Herbal - pharmacology; Endometriosis - drug therapy; Endometriosis - genetics; Endometriosis - metabolism; Female; Humans; Janus Kinase 2 - biosynthesis; Janus Kinase 2 - genetics; Retrospective Studies; Sesquiterpenes - pharmacology; Signal Transduction; STAT3 Transcription Factor - biosynthesis; STAT3 Transcription Factor - genetics; Uterus - metabolism; Uterus - pathology; Young Adult
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.934914

BACKGROUND Curcumol is a hydrogenated austenitic compound with hemiketal. In this study we evaluated the effects of curcumol on local inflammatory response, cell proliferation, and metastasis in endometriosis, and elucidated the underlying mechanisms. MATERIAL AND METHODS Ectopic endometrial stromal cells were treated with increasing doses of curcumol. The MTT assay was used to assess cell viability. FITC-labeled annexin-V/PI double-staining method and flow cytometry were used to determine cell apoptosis. Cell migration was evaluated using a wound healing assay. ELISA kits were used to detect the levels of TNF-alpha, IL-6, and IL-1ß. Western blot assay was used to examine the phosphorylation degree of JAK2 and STAT3 and the expression of Bax, Bcl2, and caspase-3 proteins. Autologous endometrial transplantation was used to establish a rat model to assess the anti-EMS effect of curcumol in vivo. RESULTS Curcumol can inhibit the proliferation of ectopic endometrial stromal cells, promote cell apoptosis, and weaken cell migration ability. Curcumol can reduce the expression of Bax and caspase-3 protein and increase the expression of Bcl2 protein. Curcumol also can inhibit the secretion of inflammatory cytokines, including tumor necrosis cytokines (TNF)-alpha, interleukin (IL)-6, and IL-1ß, by ectopic endometrial stromal cells. In addition, curcumol can also inhibit the phosphorylation of JAK2 and STAT3. In vivo experiments also proved that curcumol could inhibit the growth of ectopic lesions in EMS model rats. CONCLUSIONS Curcumol can inhibit the JAK2/STAT3 pathway, reduce the inflammatory cytokines secreted by ectopic endometrial stromal cells, inhibit cell proliferation and migration, and reduce the volume of ectopic lesions.