Carnosol is a potent Ribosomal S6 Kinase (RSK2) inhibitor that could be useful for treating gastric cancer, with an IC50 of ~5.5 μM.
It is showed that carnosol has no cytotoxic effects on GES1 cells and 10 μM carnosol strongly suppresses RSK2 activity, but has little effect on any other kinase. Carnosol exerts strong dose-dependent inhibitory effects against RSK2 autophosphorylation and phosphorylation of its substrate ATF1[1].
Results indicate that Carnosol significantly decreaseS the volume and weight of gastric tumors relative to the vehicle-treated group. Additionally, mice tolerate treatment with carnosol without significant loss of body weight similar to the vehicle-treated group. The phosphorylation of CREB, a direct downstream protein of RSK2, Is strongly inhibited in the carnosol-treated group but the expression of total CREB is relatively unchanged[1].
References:
[1]. Wang L, et al. Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2. Oncotarget. 2018 Feb 6;9(76):34200-34212.