DJ-1 mediates the resistance of cancer cells to dihydroartemisinin through reactive oxygen species removal

ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression

“…These data are in line with previous reports which also revealed that suppression of the DJ-1 protein could lead to a weakened antioxidant defense in cancer cells and enhanced efficacy of ROS-induced agents. 19,48,51 Animal studies further revealed that the ovarian cancer tumors exposed to a single dose of a combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence (Fig. 5A).…”

“…These data are in a good agreement with previous reports, which implicated DJ-1 as an intracellular sensor for oxidative stress 19 and postulated its upregulation protects cancer cells against different oxidative agents. [46][47][48][49][50][51] Furthermore, we revealed that suppression of DJ-1 protein enhances the therapeutic efficacy of PDT (Fig. 3 C and D) and this enhancement was accompanied by substantial increase of intracellular ROS level as compared to PDT alone in both cancer cell lines ( Fig.…”

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

“…performed protein expression studies using MALDI‐TOF (matrix‐assisted laser desorption/ionization–time‐of‐flight) MS and reported changes in the expression of ER stress and mitochondrial proteins following artemisinin treatment, while also characterizing differentially expressed proteins between artemisinin‐susceptible and artemisinin‐resistant HCT116 cells . In their follow‐up study, a similar methodology with a more sensitive LC‐MS/MS approach using resistant HeLa cells was applied, identifying a novel cytoprotective protein DJ‐1 (encoded by the PARK7 gene) to be significantly and consistently overexpressed in artemisinin resistant cells . DJ‐1 was subsequently shown to be protective against oxidative damage via mitochondrial translocation and ROS removal, supporting the notion that ROS and mitochondria play important roles artemisinin‐induced cell death.…”

SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

“…Among the two interactants of SG2NA, Akt has long been accepted as a nodal player in cancer cell survival [33], but the role of DJ-1 in cancer development has lately been appreciated. Available data suggest that DJ-1 is involved in multiple facets of cancer development i.e., maintenance of transformed phenotype, regulation of cell growth, survival, metastasis and resistance to chemotherapeutics [18,22,34,35]. Such wider role of DJ-1 is likely due to its diverse functions including RNA-binding, redox-regulated chaperone activity, scavenging of ROS, cysteine proteolysis and transcriptional coactivation [34,36,37].…”

“…DJ-1 activates Akt signaling by direct interaction and inhibition of PTEN [16,17]. It also can sense increased generation of reactive oxygen species (ROS); thus it acts as redox-sensitive chaperone and scavenge excess ROS, enhancing resistance against oxidative stress [18].…”