Aqueous extract of Sanguisorba officinalis blocks the Wnt/β-catenin signaling pathway in colorectal cancer cells

Abstract

Sanguisorba officinalis (the Chinese name is DiYu, DY) exerts significant anti-proliferative activities against colorectal cancer (CRC) cells. Since most of CRC result from the aberrant activation of the Wnt/b-catenin signaling pathway, inhibitors of the Wnt pathway are considered as promising anti-CRC agents. This study aimed to investigate whether DY could be a potential herbal Wnt inhibitor, and the bioactive constituents and underlying molecular mechanisms for DY's inhibiting activities would be studied as well. Accordingly, the inhibitory activities of DY and its main components against the Wnt pathway were assessed using the single-luciferase reporter assay based on HEK293 cells. Additionally, the levels of key Wnt-related genes or proteins were measured to verify the inhibitory effects on the Wnt pathway of CRC cells. Finally, the underlying mechanisms accounting for the efficacy of candidate drugs were explored by the transcriptomic study. Results show that DY and its tannins (RZ), and saponins (ZG) significantly inhibited the Wnt pathway of HEK293 cells activated by wnt3a. However, their respective constituents were not effective as expected. Additionally, DY and RZ prominently down-regulated the levels of b-catenin and Wnt-targeted genes including Axin2, c-Myc or CyclinD1 of three CRC cells. Transcriptomic profiling study suggests that the down-regulation of the mRNA levels of Wnt-related genes such as LPAR6 may be associated with the inhibitory effects of DY and RZ on the Wnt pathway of HT29 cells. Therefore, our studies first uncovered the blocking activity of DY on the Wnt pathway, providing evidence for the rationale of developing Wnt inhibitors from DY as anti-CRC agents.

Chemical composition and bioactive properties of Sanguisorba minor Scop. under Mediterranean growing conditions

“…Moreover, water extracts from the same species (S. officinalis) inhibited the signaling pathway Wnt/ β-catenin in colorectal cancer cells through down-regulation of β-catenin and Wnt-targeted genes. 16…”

Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway

“…As aberrant activation of the Wnt/β-catenin pathway is involved in cell proliferation, invasive features and development of chemoresistance resistance in cancer cells, this pathway is considered as a potential novel target of chemotherapeutic or chemopreventive agents for cancer types (15). currently, several natural agents from drug discovery platforms, including aesculetin (16), baicalin (17), hydnocarpin (15), isobavachalcone (18), jatrorrhizine (4), Sanguisorba officinalis (19) and wogonin (20), have been verified to directly or indirectly target β-catenin and its downstream signaling partners T cell-specific transcription factor/lymphoid-enhancer binding factor (TcF/LEF), consequently reducing the viability of cRc cells. However, the underlying mechanisms responsible for the effects of paeonol against cRc are yet to be fully elucidated.…”

A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

“…It has broad biological activities including anti-cancer, anti-inflammatory, and anti-oxidative activities [14]. Our previous results have proved that the aqueous extract of great burnet showed strong inhibition against proliferation of CRC cells (HCT116, RKO) [15] and Wnt/β-catenin signaling pathway [16]. However, the active compound and the underlying molecular mechanism such as apoptosis process in HT29 cells remained unknown.…”