부산대학교 도서관

Background Colorectal cancer is one of the most common cancer and the third leading cause of death worldwide. Increased generation of reactive oxygen species (ROS) is observed in many types of cancer cells. Several studies have reported that an increase in ROS production could affect the expression of proteins involved in ROS-scavenging, detoxification and drug resistance. Nuclear factor erythroid 2 related factor 2 (Nrf.sub.2) is a known transcription factor for cellular response to oxidative stress. Several researches exhibited that Nrf.sub.2 could exert multiple functions and expected to be a promising therapeutic target in many cancers. Here, Nrf.sub.2 was knocked down in colorectal cancer cell line HT29 and changes that occurred in signaling pathways and survival mechanisms were evaluated. Methods The influence of chemotherapy drugs (doxorubicin and cisplatin), metastasis and cell viability were investigated. To explore the association between specific pathways and viability in HT29-Nrf.sub.2.sup.-, proteomic analysis, realtime PCR and western blotting were performed. Results In the absence of Nrf.sub.2 (Nrf.sub.2.sup.-), ROS scavenging and detoxification potential were dramatically faded and the HT29-Nrf.sub.2.sup.- cells became more susceptible to drugs. However, a severe decrease in viability was not observed. Bioinformatic analysis of proteomic data revealed that in Nrf.sub.2.sup.- cells, proteins involved in detoxification processes, respiratory electron transport chain and mitochondrial-related compartment were down regulated. Furthermore, proteins related to MAPKs, JNK and FOXO pathways were up regulated that possibly helped to overcome the detrimental effect of excessive ROS production. Conclusions Our results revealed MAPKs, JNK and FOXO pathways connections in reducing the deleterious effect of Nrf.sub.2 deficiency, which can be considered in cancer therapy. Keywords: Nrf.sub.2, MAPK pathway, Mitochondria, Proteomics
Author(s): Omid Cheraghi[sup.1] , Bahareh Dabirmanesh[sup.1] , Farideh Ghazi[sup.2] , Massoud Amanlou[sup.3] , Mona Atabakhshi-kashi[sup.4] , Yaghoub Fathollahi[sup.5] and Khosro Khajeh[sup.1] Introduction Colorectal cancer is known as one of the [...]