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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: Mol Pharm. 2016 May 26;13(6):2070–2083. doi: 10.1021/acs.molpharmaceut.6b00205

Figure 1.

Figure 1

Schematic illustration of the dendrimer-based nanoplatform for targeted delivery of DJ-1 siRNA to the ovarian cancer cells via LHRH receptor-mediated endocytosis and the role of siRNA-induced suppression of DJ-1 protein in the combinatorial treatment. siRNA-mediated knockdown prevents DJ-1 protein from (A) inhibiting the PTEN expression, thereby promoting phosphorylation of Akt and activating cell proliferation and migration; (B) suppressing p53 transcriptional activity, therefore inhibiting the apoptotic p53-Bax-caspase pathway and cell cycle arrest functionality; (C) protecting cancer cells from intrinsic oxidative stress and the consequent ROS-mediated apoptosis. DJ-1 facilitates GSH synthesis via upregulation of the rate-limiting enzyme glutamate cysteine ligase (GCL). In addition, DJ-1 stabilizes NRF2, which is responsible for both GSH recycling via modulating the activity of glutathione reductase (GR) and transcriptional activation of various antioxidant proteins.