Multi-target tracheloside and doxorubicin combined treatment of lung adenocarcinoma.

Chemotherapy is one of the main methods for malignant lung cancer treatment. However, the side effects of chemotherapy drugs are serious and it is prone to drug resistance. Therefore, multi-drug combination chemotherapy is popular in lung cancer treatment. This study found that tracheloside (TCS) was a novel inhibitor of TMEM16A which was specific high expressed in lung cancer tissues. TCS concentration dependently inhibited TMEM16A with an IC50 of 3.09 ± 0.21 µM. It inhibited lung cancer cells proliferation, migration, and induced cells apoptosis targeting TMEM16A. In addition, molecular docking combined with site-directed mutagenesis confirmed that the binding sites of TCS to TMEM16A were S387, E623, E624. Subsequently, multi-target combined drug administration was conducted based on the different drug targets of TCS and doxorubicin (DOX). Both in vitro and in vivo experiments indicated that the combined administration of low concentration of TCS and DOX achieved satisfactory anticancer effect, and it offset the side effects caused by high concentration of DOX. Therefore, TCS is a safe and efficient anticancer lead compound which can enhance the effect of DOX.

In Vivo and In Vitro Effects of Tracheloside on Colorectal Cancer Cell Proliferation and Metastasis.

Recent research suggests a relationship between cancer progression and oxidative mechanisms. Among the phenolic compounds such as tracheloside (TCS) are a major bioactive compound that can combat oxidant stress-related chronic diseases and that also displays anti-tumor activity. Although TCS can inhibit mammalian carcinoma, its effects on colorectal cancer (CRC) have not been clarified. The purpose of this study was to investigate the effects of TCS on the proliferation of CRC cells, the metastasis of CT26 cells, and the molecular mechanisms related to TCS in vitro and in vivo. A cell viability assay showed that TCS inhibited the proliferation of CRC cells. TCS-treated CT26 cells were associated with the upregulation of p16 as well as the downregulation of cyclin D1 and CDK4 in cell cycle arrest. In addition, TCS induced apoptosis of CT26 cells through mitochondria-mediated apoptosis and regulation of the Bcl-2 family. Expression of epithelial-mesenchymal transition (EMT) markers was regulated by TCS treatment in CT26 cells. TCS significantly inhibited the lung metastasis of CT26 cells in a mouse model. These results suggest that TCS, by inducing cell cycle arrest and apoptosis through its anti-oxidant properties, is a novel therapeutic agent that inhibits metastatic phenotypes of murine CRC cells.