A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be responsible for tumor relapse and resistance to conventional chemotherapy. The development of a non-toxic, natural treatment for the elimination of CSCs is considered a strategy for cancer treatment with minimal side effects. In the present study, the potential for Sasa quelpaertensis leaf extract (SQE) and its two bioactive compounds, tricin and p-coumaric acid, to exert anti-CSC effects by suppressing cancer stemness characteristics were evaluated in colon cancer cells. CD133+CD44+ cells were isolated from HT29 and HCT116 cell lines using flow-activated cell sorting (FACs). SQE treatment was found to significantly suppress the self-renewal capacity of both cell lines. SQE treatment was also associated with the down-regulation of β-catenin and phosphorylated GSK3β, while significantly enhancing cell differentiation by up-regulating CK20 expression and blocking the expression of several stem cell markers, including DLK1, Notch1, and Sox-2. In vivo, SQE supplementation suppressed tumor growth in a xenograft model by down-regulating stem cell markers and β-catenin as well as HIF-1α signaling. Compared with two bioactive compounds of SQE, SQE exhibited the most effective anti-CSC properties. Taken together, these results provide evidence that SQE inhibits colon cancer by regulating the characteristics of CSCs.
BACKGROUND/OBJECTIVESInflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment.MATERIALS/METHODSAn in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation.RESULTSTreatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), IL-6, and IL-1β in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α were down-regulated in response to inhibition of IκBα phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties.CONCLUSIONSSQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.
Colon cancer is a leading cause of cancer death in worldwide. Most colon cancer patients develop recurrence suggesting that colon cancer is driven by a subpopulation of self‐renewing cancer cells, termed cancer stem cell (CSCs), which may be responsible for tumor relapse and resistance against chemotherapy. Targeting CSCs to treat colon cancer may be an important therapeutic strategy. Sasa quelpaertensis Nakai is a bamboo grass that only grows in Jeju Island in South Korea. Although the anti‐obesity and anti‐inflammatory effects of Sasa leaves have been reported, the anti‐cancer stem cell effects of Sasa leaves remain unknown. The aim of this study was to investigate the effects of Sasa quelpaertensis leaves extracts (SQE) on suppressing cancer stemness of colon cancer cell. To obtain CSCs, we isolated CD133+/CD44+ population of HT29 colon cancer cells using Flow Cytometry Cell Sorting (FACS). We found that SQE significantly suppressed CD133+ and CD44+ population using FACS analysis. SQE inhibited colony formation and nonadherent sphere formation which are characteristics of cancer stem cells. SQE down‐regulated expressions of CSC markers, including SOX‐2, Notch1, DLK1, and b‐catenin. Furthermore, SQE down‐regulated the expression of HIF‐1α, and its down‐stream gene, VEGF. In conclusion, SQE has an important role in regulating colon cancer stemness by suppressing self‐renewal potential and CSC markers, thereby contributes to the overall inhibition of cancer cell growth.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.