Tanshinone IIA (Tan-IIA) suppresses the proliferation and migration of cholangiocarcinoma cells and induces their apoptosis, according to the findings of a new study published in Scientific Reports.
“Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of [cholangiocarcinoma],” the authors wrote.
Tan-IIA is a compound extracted from Danshen, a traditional Chinese medicine that has been reported to have pharmacological effects on cancer. Previous research has shown that Tan-IIA has anticancer potential in hepatocellular carcinoma and pancreatic cancer. However, its mechanism of action is unknown.
Read more about cholangiocarcinoma therapies
To find the target of Tan-IIA in cholangiocarcinoma and investigate its possible mechanism of action, a team of researchers from Qingdao University and Dalian Medical University in China used a cyberpharmacology approach.
They combined Tan-IIA and cholangiocarcinoma-specific targets with protein-protein interactions to construct a Tan-IIA-cholangiocarcinoma network. By applying a network pharmacology approach, they identified potential targets and mechanisms of Tan-IIA to treat cholangiocarcinoma.
The researchers then investigated the anticancer effects of Tan-IIA using a mouse model and human cholangiocarcinoma cell lines in vitro.
They found that Tan-IIA inhibited the expression of PI3K, p-Akt, p-mTOR, and mTOR, which are parts of the most common aberrant kinase cascade signaling pathway that promotes tumor cell proliferation. In a reverse experiment, the researchers showed that treatment with a PI3K agonist dramatically reduced the anticancer effects of Tan-IIA.
The researchers also showed that Tan-IIA treatment downregulated the levels of Bcl2 and increased the expression of cleaved caspase-3, which ultimately induced cholangiocarcinoma cell apoptosis.
They concluded that Tan-IIA inhibits the malignant growth of cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway and could be a potent agent for the treatment of the disease.
Liu H, Liu C, Wang M, et al. Tanshinone IIA affects the malignant growth of cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway. Sci Rep. 2021;11(1):19268. doi:10.1038/s41598-021-98948-z