Fig. 5.

The mechanisms underlying tanshinone IIA-TRAIL synergy. Tanshinone IIA sensitizes TRAIL-resistant epithelial ovarian cancer (EOC) cells to TRAIL-induced apoptosis through at least two mechanisms. First, tanshinone IIA evokes ROS-dependent activation of JNK to increase CHOP expression, which in turn activate DR5 transcription to up-regulate cell-surface DR5 levels for the potentiation of TRAIL-induced apoptosis stimuli. Second, tanshinone IIA engages the p38 MAPK-mediated pathway to induce transcriptional down-regulation of survivin, consequently promoting caspase activities to execute apoptosis.