Brusatol can inhibit proliferation and suppress the epithelial-mesenchymal transition process in intrahepatic cholangiocarcinoma (iCCA) oncocytes, according to a new study published in Phytomedicine. Researchers obtained the results in iCCA cell function experiments followed by verification in a mouse model.

“Brusatol is a quassinoid extracted from the seeds of Brucea sumatrana and has been developed as an experimental treatment for human malignancies such as those of leukemia, lung cancer, and pancreatic carcinoma,” the authors said.

“This study is the first to explore the therapeutic potential of brusatol in [iCCA] and its possible molecular mechanisms and provides promising evidence and a theoretical basis for the clinical application of brusatol in human patients with [iCCA].”


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The research team employed quantitative reverse transcription-polymerase chain reaction and Western blot with iCCA cells to confirm the ability of brusatol to suppress the epithelial-mesenchymal transition process at the gene transcription and protein translation levels. They were also able to demonstrate brusatol’s ability to inhibit the proliferation, migration, and invasion of iCCA oncocytes via wound healing and Matrigel invasion studies.

Finally, the team employed a nude mouse model of subcutaneous tumors along with in vitro iCCA cell function experiments to confirm the antitumor effect of brusatol.

The authors suspect that these effects are mediated by inhibition of the PI3K/Akt/mTOR pathway, given that the differentially expressed genes in their experiments were highly enriched in PI3K/Akt/mTOR signaling pathway-related indicators. They also found that the PI3K/AKT pathway was able to partially reverse the antitumor effects of iCCA oncocytes, further supporting the iCCA growth inhibitory capability of brusatol.

They hope their study results lay a foundation for further prospective clinical and experimental studies to assess the safety and efficacy of brusatol in human patients with iCCA.

Reference

Chen Z, He B, Zhao J, et al. Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway. Phytomed. Published online July 6, 2022. doi:10.1016/j.phymed.2022.154323