Pyrvinium pamoate inhibits proliferation and invasion of human endometriotic stromal cells

2019 ◽  
Vol 39 (5) ◽  
pp. 662-672
Author(s):  
A Karamian ◽  
H Nazarian ◽  
SA Ziai ◽  
A-H Zarnani ◽  
S Salehpour ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Migration And Invasion ◽  
Endometrial Stromal Cells ◽  
Anticancer Effects ◽  
And Control ◽  
Proliferation And Invasion ◽  
Pyrvinium Pamoate

Endometriosis is characterized by the presence of functional endometrial tissue in other pelvic organs. This gynecologic problem occurs in 35–50% of women with pain and infertility. Endometriotic cells share some characteristics such as proliferation, migration, and invasion with tumor cells. Pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration, could inhibit the Wnt/β-catenin signaling pathway and its anticancer effects were examined by several researchers. In this study, 12 ectopic and eutopic endometrial biopsies from females with ovarian endometrioma and 12 endometrial biopsies from nonendometriotic females were obtained. Ectopic (EESCs), eutopic (EuESCs), and control (CESCs) endometrial stromal cells were isolated. Then, the effect of pyrvinium pamoate on the proliferation and invasiveness of in vitro cultured cells was evaluated. The proliferation of CESCs, EuESCs, and EESCs was significantly decreased after treatment with pyrvinium pamoate. In addition, treatment with pyrvinium pamoate significantly inhibited the invasiveness of CESCs, EuESCs, and EESCs compared to nontreated groups. The results of the present research showed that pyrvinium pamoate inhibits the proliferation and invasion of human endometriotic stromal cells in vitro, further investigations on the therapeutic potential of this compound in endometriosis are required.

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells

2020 ◽  
pp. 096032712096454
Author(s):  
Amin Karamian ◽  
Shahrokh Paktinat ◽  
Sahar Esfandyari ◽  
Hamid Nazarian ◽  
Seyed Ali Ziai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Chronic Inflammatory Disease ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Mrna Gene ◽  
And Control ◽  
Mrna Gene Expression ◽  
Pyrvinium Pamoate

Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10–15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/β-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.

scholarly journals The scar constituent Collagen I triggers coordinated collective migration and invasion in a 3D spheroid model of early endometriotic lesions

2020 ◽  
Author(s):  
Anna Stejskalova ◽  
Victoria Fincke ◽  
Melissa Nowak ◽  
Yvonne Schmidt ◽  
Marie-Kristin von Wahlde ◽  
...  
Keyword(s):  
Stromal Cells ◽  
3D Model ◽  
Single Cells ◽  
Experimental Models ◽  
Collagen I ◽  
Migration And Invasion ◽  
Collective Migration ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells

AbstractEndometriosis is a painful gynaecological condition characterized by ectopic growth of endometrial cells outside of the uterus. Little is known about the mechanisms by which endometrial fragments invade tissues. This is partially due to a lack of suitable experimental models. In this study, we show that a spheroid 3D model, but not single cells mimic the collective endometrial fragment-like invasion through the extracellular matrix. This model reveals that collagen I, the main constituent of surgical scars, significantly increases the rate of lesion formation by healthy endometrial stromal cells (St-T1b) in vitro compared to the basement membrane-like matrix Matrigel. Stromal cell invasion of collagen I requires MMPs, whereas collective migration of endometriotic epithelial 12Z cells involves Rac-signalling. We show that inhibiting ROCK signalling responsible for actomyosin contraction increases the lesion-size. Moreover, endometriotic epithelial 12Z cells, but not eutopic stromal cells St-T1b migrate on Matrigel. The rate of this migration is decreased by the microRNA miR-200b and increased by miR-145. Our 3D model offers a facile approach to dissect how endometrial fragments invade tissues and is an important step toward developing new personalized therapeutics for endometriosis. Moreover, our model is a suitable tool to screen small molecule drugs and microRNA-based therapeutics.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals Endometrial regeneration with endometrial epithelium: homologous orchestration with endometrial stroma as a feeder

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryo Yokomizo ◽  
Yukiko Fujiki ◽  
Harue Kishigami ◽  
Hiroshi Kishi ◽  
Tohru Kiyono ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Stromal Cells ◽  
Therapeutic Option ◽  
Three Dimensional ◽  
Fertility Treatment ◽  
Feeder Cells ◽  
Endometrial Stromal Cells ◽  
Thin Endometrium ◽  
Endometrial Epithelial Cells

Abstract Background Thin endometrium adversely affects reproductive success rates with fertility treatment. Autologous transplantation of exogenously prepared endometrium can be a promising therapeutic option for thin endometrium; however, endometrial epithelial cells have limited expansion potential, which needs to be overcome in order to make regenerative medicine a therapeutic strategy for refractory thin endometrium. Here, we aimed to perform long-term culture of endometrial epithelial cells in vitro. Methods We prepared primary human endometrial epithelial cells and endometrial stromal cells and investigated whether endometrial stromal cells and human embryonic stem cell-derived feeder cells could support proliferation of endometrial epithelial cells. We also investigated whether three-dimensional culture can be achieved using thawed endometrial epithelial cells and endometrial stromal cells. Results Co-cultivation with the feeder cells dramatically increased the proliferation rate of the endometrial epithelial cells. We serially passaged the endometrial epithelial cells on mouse embryonic fibroblasts up to passage 6 for 4 months. Among the human-derived feeder cells, endometrial stromal cells exhibited the best feeder activity for proliferation of the endometrial epithelial cells. We continued to propagate the endometrial epithelial cells on endometrial stromal cells up to passage 5 for 81 days. Furthermore, endometrial epithelium and stroma, after the freeze-thaw procedure and sequential culture, were able to establish an endometrial three-dimensional model. Conclusions We herein established a model of in vitro cultured endometrium as a potential therapeutic option for refractory thin endometrium. The three-dimensional culture model with endometrial epithelial and stromal cell orchestration via cytokines, membrane-bound molecules, extracellular matrices, and gap junction will provide a new framework for exploring the mechanisms underlying the phenomenon of implantation. Additionally, modified embryo culture, so-called “in vitro implantation”, will be possible therapeutic approaches in fertility treatment.

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