Abstract
Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. Here, we investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells. Immunohistochemistry was used to examine protein expression and cell purity. Quantitative RT-PCR was conducted to assess mRNA expression, and Western blot was performed to determine protein level. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Glycolysis and mitochondrial function were evaluated by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) of cells, respectively. Lastly, plasmid transfection and inhibitor treatment were used for overexpression and inhibition studies. Cinnamic acid inhibited cell viability and cell invasion, as well as decreased ECAR and OCR, in primary endometrial stromal cells. Cinnamic acid suppressed the effects of PKM2 overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid. Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2. Our study identified cinnamic acid as a novel compound from Cinnamomum cassia Presl that displays potent effects on primary endometrial stromal cell viability, invasion, and glycolysis, suggesting its potential use for endometriosis treatment.
Highlights
Endometriosis is a gynecological disorder that affects at least 10% of women of reproductive age worldwide [1, 2] and features abnormal growth of endometrial tissues and stroma-like lesions outside the uterus
Cinnamic acid suppressed the effects of Pyruvate kinase isoform 2 (PKM2) overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid
Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2
Summary
Endometriosis is a gynecological disorder that affects at least 10% of women of reproductive age worldwide [1, 2] and features abnormal growth of endometrial tissues and stroma-like lesions outside the uterus. Recent findings have shown that women with endometriosis exhibit a shift in cell metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis in the peritoneal microenvironment [6, 7]. Transforming growth factor beta (TGF-β) has been implicated in the etiology of peritoneal endometriosis [8]. TGF-β is known induce the conversion of glucose to lactate via glycolysis, a process known as the “Warburg effect” [9-11], resulting in cell invasion and angiogenesis, both of which are crucial steps in endometriosis pathophysiology. Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. We investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells
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