. Role of ROS and enhanced NEAPP-AM sensitivity with BSO Subsequently, we examined whether ROS produced by NEAPP have anti-tumor effects. To test the role of ROS in NEAPP-AM treatment, NOS2 cells were pre-incubated with NAC or BSO, followed by the addition of NEAPP-AM for the indicated exposure time. The viability of NOS2 cells was assayed 24 hours after NEAPP-AM treatment using the cell viability assay. As shown in Fig. 3, the growth-inhibitory effects of NEAPP-AM-180 were completely inhibited on being pretreated with NAC, while the viability decreased by roughly 30% after NEAPP-AM-300 with NAC, indicating that there might be insufficient molecules of NAC 5 Plasma Therapy for Chemoresistant Ovarian Cancer reduced to 9% after NEAPP-AM-120 treatment, being more sensitive to NEAPP-AM. In addition, a similar tendency was noted in other NOS3TR and NOS3CR cells. Growth-inhibitory effect of NEAPP-AM on tumor xenografts in mouse model We finally investigated the potential anti-tumor properties of NEAPP-AM in nude mice receiving subcutaneous xenografting. The experimental conditions of this in vivo model were set to assess whether NEAPP-AM could inhibit tumor formation due to microdissemination. Subcutaneous tumor formation was observed at least approximately 10 days after the inoculation of mice with NOS2 or 2883-98-9 biological activity NOS2TR cells. Subsequently, periodic s.c. treatment 7884917 with NEAPP-AM was performed, as described in Materials and Methods. As shown in Fig. 8, the calculated tumor volumes on day 28 were 3006136 and 163691 in the NOS2 and NOS2TR control groups and 55660 and 104666 in the NOS2 and NOS2TR groups treated with NEAPP-AM, respectively. NEAPP-AM injection resulted in an average inhibition of NOS2 cell-inoculated tumor weight by 66% and NOS2TR cell-inoculated tumors by 52%, as compared with the control. Accordingly, NEAPPAM significantly reduced 
the growth of both parental and chemoresistant EOC tumors. During the experiment, we confirmed that the NEAPP-AM administration was nontoxic by observing mouse weights, survival, and behavior, and no complications such as anaphylaxis and skin necrosis were detected. We also observed histological differences in the tumor sections between NEAPP-AM-treated and -untreated groups in both cell lines. It should be noted that papillary growth, a clear character in ovarian serous adenocarcinoma from which NOS2 and NOS2TR were isolated, was detected. On the contrary, NEAPP-AM-treated A mechanism of NEAPP-AM-induced apoptosis on NOS2 and NOS2TR cells In our previous study, direct NEAPP treatment induced cell apoptosis in EOCs. We subsequently assessed whether the cytotoxic effect of NEAPP-AM was associated with the induction of apoptosis. Caspase-3/7 activity was assayed at 4 hrs after NEAPP-AM treatment by loading the fluorescent substrate CellEventTM caspase-3/7 Green Detection Reagent. As expected, compared with control cells, NEAPP-AM treatment caused 14579267 morphological changes,which were typical of apoptosis, and the activation of caspase3/7 in both cell types. These results suggest that NEAPP-AM induced apoptosis through caspase-3/7 activation. Furthermore, it has been reported that NEAPP treatment upregulates the production of intracellular ROS, leading to the apoptosis in cancer cells. In order to determine the role of ROS plays in NEAPP-AM induced apoptosis, we first examined the production of ROS using the oxidant-sensitive fluorescent probe CM-H2DCFDA. The results revealed that treatment with NEAPP-AM increased th
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