Natural product pectolinarigenin exhibits potent anti-metastatic activity in colorectal carcinoma cells in vitro and in vivo

• Published in: Bioorganic & medicinal chemistry 2019-11, Vol.27 (21), p.115089-115089, Article 115089
• Main Authors: Gan, Cailing, Li, Yali, Yu, Yan, Yu, Xi, Liu, Hongyao, Zhang, Qianyu, Yin, Wenya, Yu, Luoting, Ye, Tinghong
• Format: Article
• Language: English
• Subjects: Apoptosis; Colorectal cancer; MDSCs; Metastasis; Pectolinarigenin
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2019.115089

[Display omitted] •Pectolinarigenin could inhibit CRC cell growth and induce apoptosis.•Pectolinarigenin impaired CRC cell metastasis via MMPs signalling pathway.•Pectolinarigenin impaired CRC cell metastasis by down-regulating p-Stat3Tyr705.•Pectolinarigenin inhibit tumour metastasis by reducing the number of MDSCs cells. Colorectal carcinoma (CRC) is one of the most common cancers with high metastatic potential, explaining why identifying new drug candidates that inhibit tumour metastasis is an urgent need. The aim of this study was to evaluate the biological activities of pectolinarigenin (PEC, a natural flavonoid present in Cirsium chanroenicum) in CRC in vitro and in vivo and to determine its underlying mechanism of action. Here, we observed that treatment with PEC could inhibit cell viability and induce apoptosis in cancer cells in a concentration- and time-dependent manner. The occurrence of apoptosis was associated with activation of caspase-3 and Bax and decreased expression of Bcl-2. In addition, PEC markedly impaired CRC cell migration and invasion by downregulating the expression of matrix metalloproteinase (MMP-9) and phosphorylated-Stat3Tyr705. Moreover, our studies showed that PEC inhibited abdominal metastasis models of murine colorectal cancer. In addition, histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, MMP9-positive cells and p-Stat3Tyr705 cells upon treatment with PEC compared to control samples. Furthermore, PEC reduced the number of myeloid-derived suppressor cells (MDSCs) in the blood and tumours, which was accompanied by the increased infiltration of CD8+T cells in the blood. Taken together, our findings suggested that PEC could be used as a natural drug to inhibit CRC metastasis.