Delphinidin enhances radio-therapeutic effects via autophagyinduction and JNK/MAPK pathway activation in non-small celllung cancer

ABSTRACT

Delphinidin is a major anthocyanidin compound found in various vegetablesand fruits. It has anti-oxidant, anti-inflammatory, and various other biologicalactivities. In this study we demonstrated the anti-cancer activity of delphinidin,which was related to autophagy, in radiation-exposed non-small cell lung cancer(NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxicdose of delphinidin (5 M) before exposure to -ionising radiation (IR). Wefound that treatment with delphinidin or IR induced NSCLC cell death in vitro; howeverthe combination of delphinidin pre-treatment and IR was more effective thaneither agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethaldose. Moreover, combined treatment with delphinidin and IR, enhanced apoptoticcell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway.Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increasedthe expression of autophagy-induced cell death associated-protein in radiation-exposedNSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidinpre-treatment in radiation-exposed NSCLC cells. Collectively, these results show thatdelphinidin acts as a radiation-sensitizing agent through autophagy induction andJNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.