Marine alkaloid monanchoxymycalin C: a new specific activator of JNK1/2 kinase with anticancer properties.

摘要: Monanchoxymycalin C (MomC) is a new marine pentacyclic guanidine alkaloid, recently isolated from sponge Monanchora pulchra by us. Here, anticancer activity and mechanism of action was investigated for the first time using human prostate cancer (PCa) model. MomC active in all PCa cell lines at low micromolar concentrations induced an unusual caspase-independent, non-apoptotic death. Kinase screening identified activation mitogen-activated protein kinase (MAPK) c-Jun N-terminal (JNK1/2) to be one primary molecular activity. Functional assays demonstrated specific selective JNK1/2 prior induction other death related processes. Inhibition pretreatment with JNK-inhibitor SP600125 antagonized cytotoxic compound. caused upregulation ROS. However, contrast ROS-inducing agents, co-treatment PARP-inhibitor olaparib revealed antagonistic effects indicating PARP necessary Interestingly, although no direct regulation p38 ERK1/2 were detected, required efficacy, while inhibition increased its cytotoxicity. In conclusion, shows promising against PCa, which exerted via