Abstract
The proliferation and migration of intestinal epithelial cell is important to the barrier integrity of intestinal epithelium. Cucurbitacin E (CuE) is one of the tetracyclic triterpenoids extracted from the cucurbitaceae that has been shown to inhibit cancer cell growth, tumor angiogenesis and inflammatory response. Nevertheless, the role of Cucurbitacin E in regulating the proliferation and migration of intestinal epithelial cells remain unclear. In this study, the human intestinal epithelial cell line Caco-2 was treated with CuE and the effects of CuE on cell cycle, proliferation, migration and actin dynamics in Caco-2 cells were investigated successively. We found that CuE significantly inhibited the cell proliferation and migration, inducing the cell cycle arrest in G2/M phase and disrupting the actin dynamic balance in Caco-2 cells. Finally, we showed that CuE inhibited cofilin phosphorylation by suppressing the phosphorylation of both LIM kinase (LIMK)1 and LIMK2 in vitro, resulting in the activation of cofilin, which is closely associated with cell proliferation and migration. Therefore, our studies provided the first evidence that CuE inhibited the proliferation and migration of intestinal epithelial cells via activating cofilin, and CuE is a potential candidate in intestinal disease therapy.
Highlights
Cell proliferation and migration plays an important role in intestinal epithelial repairment when it is damaged, such as by inflammatory bowel disease, ulcers, infections, radiation, or chemotherapy (Ciorba et al, 2012; Mokry et al, 2014; Zuo et al, 2015; Coch and Leube, 2016; Ramanan and Cadwell, 2016)
Based on the afore-mentioned finding that the Cucurbitacin E (CuE) inhibits the proliferation of Caco-2 cells, we further investigated the effect of CuE on cell cycle in Caco-2 cells
It is indicated that CuE is capable of causing G2/M phase arrest in intestinal epithelial cells
Summary
Cell proliferation and migration plays an important role in intestinal epithelial repairment when it is damaged, such as by inflammatory bowel disease, ulcers, infections, radiation, or chemotherapy (Ciorba et al, 2012; Mokry et al, 2014; Zuo et al, 2015; Coch and Leube, 2016; Ramanan and Cadwell, 2016). It has been well recognized that the cytoskeleton plays a critical role during the processes of cell proliferation and migration. A key component of the cytoskeleton, is involved in the transportation of intracellular materials and muscle contraction and in cell migration and cytokinesis (Mitsushima et al, 2010; Lancaster and Baum, 2014). Cofilin is a ubiquitous actin binding protein, containing an actin-depolymerizing factor homology domain, which enables stoichiometric binding of cofilin to both F- and G-actin (Pope et al, 2004). By severing the actin filaments to regulate the polymerization and depolymerization of actin, cofilin plays critical roles in the regulation of actin dynamics during cell development, migration, and tumor metastasis in a variety of cells (Samstag et al, 2013; Wu et al, 2016).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
