Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/β-catenin signaling pathway

Abstract

Studies have indicated that trichosanthin (TCS), a bioactive protein extracted and purified from the tuberous root of Trichosanthes kirilowii (a well-known traditional Chinese medicinal plant), produces antitumor effects on various types of cancer cells. However, the effects of TCS on glioma cells are poorly understood. The objective of this study was to investigate the antitumor effects of TCS on the U87 and U251 cell lines. The in vitro effects of TCS on these two cell lines were determined using a Cell Counting Kit-8 (CCK-8) assay, Annexin V-FITC staining, DAPI staining, Transwell assays, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacar-bocyanine iodide (JC-1) staining and western blotting, which was utilized to assess the expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and key proteins in the Wnt/β-catenin signaling pathway. Our data indicated that TCS inhibited the proliferation of glioma cells in a dose- and time-dependent manner and played a role in inhibiting glioma cell invasion and migration. Additional investigation revealed that the expression levels of LGR5 and of key proteins in the Wnt/β-catenin signaling pathway were markedly decreased after TCS treatment. The results suggest that TCS may induce apoptosis in glioma cells by targeting LGR5 and repressing the Wnt/β-catenin signaling pathway. In the future, in vivo experiments should be conducted to examine the potential use of this compound as a novel therapeutic agent for gliomas.

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

“…The garlic‐derived organosulfur compound diallyl trisulfide (DATS) blocks the activity of Wnt/β‐catenin pathway, consequently repressing proliferation, invasion, and angiogenesis of glioma cells (Q. Tao et al, ). Coincidently, trichosanthin (TCS) is extracted from traditional Chinese medicinal plant that contributes to glioma progression by reducing Wnt/β‐catenin signaling (Miao et al, ). As the normally consumed cruciferous vegetables, sulforaphane (SFN) effectively increases TMZ‐induced apoptosis because of downregulation of miR‐21 through Wnt/β‐catenin signaling in GBM (Lan, Pan, Yu, & Yue, ).…”

Temporal and Spatial Expression of LGR5 After Acute Spinal Cord Injury in Adult Rats

“…In the lineage tracing of mice, the LGR5 gene promoter was connected to the lacZ gene, which suggested that all the villous epithelial cells rooted from the LGR5-positive cells in the crypt, which lead to an affirmation that the intestinal stem cells are involved in the LGR5-positive cells [18,19]. In addition, in normal intestine, genetic transformation of LGR5-positive cells has revealed their potential to be tumor-initiating cells [20]. As is known to all, Wnt/β-catenin pathway, as a classic (Vector Laboratories, Burlingame, CA, USA).…”

TKP, a serine protease extracted from Trichosanthes kirilowii, inhibits the migration and invasion of colorectal adenocarcinoma cells by targeting Wnt/β‐catenin and Hedgehog/Gli1 signalings

“…Novelty, many biologically active ingredients of T. kirilowii were found to play important roles in lipid metabolism, anti‐inflammatory activity, and hypoglycemic activity (Iwabuchi, Kohno‐Murase, & Imamura, ; Shidoji & Ogawa, ). In addition, proteins extracted from T. kirilowii exert antitumor biological function (Li, Li, Zhang, Wang, & Zhang, ; Miao et al, ; Shaw, Lee, & Wong, ; Shi, Wong, & Shaw, ). TKP is a serine protease protein extracted from the fruit of T. kirilowii .…”