Cyanidin-3-O-glucoside represses tumor growth and invasion in vivo by suppressing autophagy via inhibition of the JNK signaling pathways

Abstract

Black bean seed coat extract (BBSCE) contains a high amount of bioactive compounds which can reduce the risk of cancers, but the underlying mechanism remains poorly understood in vivo. Here using a Drosophila model of a malignant tumor, wherein the activated oncogene Raf (Raf^GOF) cooperates with loss-of-function mutations in the conserved tumor suppressor scribble (scrib^−/−), we investigated the antitumor mechanism of BBSCE and its main active component cyanidin-3-O-glucoside (C3G) in vivo. The results showed that supplementation of either BBSCE or C3G inhibited the tumor growth and invasion of Raf^GOFscrib^−/− and extended their survival in a dose dependent manner. Strikingly, the activation of both autonomous and non-autonomous autophagy in tumor flies was significantly reduced by C3G treatment. A further study indicated that C3G exhibited an antitumor effect in vivo by blocking autophagy both in tumor cells and in its microenvironment by inhibiting the JNK pathway. Interestingly, the efficacy of chloroquine (CQ, an autophagy inhibitor used as an antitumor agent) combined with C3G is much better than either C3G or CQ treatment alone. C3G may be combined with CQ to treat cancers and to provide a theoretical basis for functional food or natural medicine development.