Brevilin A is a sesquiterpene lactone that has been found in C. minima and has anticancer activity.1 It is an inhibitor of STAT3 signaling (IC50 = 10.6 ?M in A549R cells) that inhibits the tyrosine kinase activity of the JAK1, JAK2, JAK3, and JAK4 JH1 subunit (IC50s = 11.2, 8.4, 10.2, and 11.9 ?M, respectively).2 It inhibits proliferation of a variety of cancer cells, including A549 lung, HepG2 liver, HeLa cervical, A875 melanoma, and CT26 mouse colon carcinoma cells in a concentration-dependent manner.1 Brevilin A (1-4 ?g/ml) decreases the mitochondrial membrane potential, induces apoptosis, and increases the level of reactive oxygen species (ROS) in CT26 cells. It also induces autophagosome formation in CT26 cells, an effect that can be blocked by the PI3K inhibitor 3-methyladenine . Brevilin A (5 mg/kg per day) increases intratumor expression of the autophagy marker LC3-II and reduces tumor growth in a murine CT26 colon cancer model.
1.You, P., Wu, H., Deng, M., et al.Brevilin A induces apoptosis and autophagy of colon adenocarcinoma cell CT26 via mitochondrial pathway and PI3K/AKT/mTOR inactivationBiomed. Pharmacother.98619-625(2018) 2.Chen, X., Du, Y., Nan, J.X., et al.Brevilin A, a novel natural product, inhibits janus kinase activity and blocks STAT3 signaling in cancer cellsPLoS One8(5)e63697(2013)