Nuclear transcription factor Nrf2 suppresses prostate cancer cells growth and migration through upregulating ferroportin

Abstract

VTo investigate the effect of nuclear transcription factor Nrf2 on the transcription of Ferroportin (FPN) in prostate cancer cells, and the regulation mechanisms of FPN on cell viability, migration and apoptosis of prostate cancer cells.Empty vectors, pEGFPC1-Nrf2, pEGFPC1-FPN, Si-FPN and Si-Nrf2 were transfected into prostate cancer cell line PC3. The expression of mRNA and protein were measured by real time-PCR (RT-PCR) and western blot. Cell viability, migration, cycle and apoptosis were tested by CCK-8 assay, wound healing and flow cytometry, respectively. The interaction between FPN and Nrf2 was confirmed by chromatin immunoprecipitation (CHIP) assay.The viability, migration and mitosis of PC3 cells could be repressed by over-expressed FPN, with decreased intracellular ferritin. The CHIP assay demonstrated that Nrf2 is one transcription factor of FPN and promotes its transcription. With the increase of Nrf2 in PC3 cells, the viability, migration ability and concentration of ferritin were suppressed, while the apoptosis rate was increased. The above effects were counteracted by down-regulating FPN.FPN could inhibit the prostate cancer cell viability, migration and mitosis, which is also related to a decrease of intracellular ferritin content. In conclusion, Nrf2 suppresses prostate cancer cells viability, migration, and mitosis through upregulating FPN.

Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways

“…Moreover, AMPK and SIRT1 can regulate transcription factors, such as Nrf2 and NF-κB, which are involved in regulating antioxidant genes against oxidative damage and the suppression of pro-inflammatory cytokines, respectively [39,40,42]. Nrf2, which is an essential transcription factor for expression of antioxidant genes, is another important modulator of the intracellular adaptive antioxidant response to oxidative stress [33,34]. Nrf2 binds to specific DNA sequence antioxidant responsive element (ARE) and stimulates the transcription of downstream target genes, antioxidant genes, including CAT, SOD, and GPX.…”

“…The inhibition of CYP2E1 activity has been shown to result in successful recovery of ethanol-induced fatty liver [32]. Nuclear factor E2-related factor 2 (Nrf2) is another important regulator of the intracellular adaptive antioxidant response to oxidative stress [33][34][35]. In addition, alcohol exposure is shown to induce hepatic lipid accumulation in Nrf2-null mice [36], and the activation of Nrf2 was able to successfully prevent alcohol-induced fatty liver [37].…”

Chemoprevention of Prostate Cancer by Natural Agents: Evidence from Molecular and Epidemiological Studies

“…It has been shown that resveratrol exerts potent anti-initiation, anti-promotion and antiprogression activities throughout the multi-stage process of carcinogenesis (153). Resveratrol can augment cellular antioxidant defence capacity and sensitise prostate cancer cells to treatment through reducing both undesired basal reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as inducing antioxidant enzymes such as heme-oxygenase-1 (HO-1) through ARE-mediated transcriptional activation of Nrf2 (156)(157)(158). In addition to its inhibition of COX-2 expression, resveratrol has been found to interfere with proinflammatory signalling pathways triggered by IL1-β leading to inhibition of inflammation, which is often involved in cancer onset and progression by regulating proliferation, apoptotic cell death and angiogenesis (159).…”

Crosstalk between Nrf2 and YAP contributes to maintaining the antioxidant potential and chemoresistance in bladder cancer

“…A well-established YAP role on physiological cellular behavior, is its action on cell migration which is related in oncology field to the invasion and the metastatic capability of tumor cells [30][31][32]. In addition, some data indicated that Nrf2 suppression also reduced the migration in different tumor cells [33][34]. To verify whether the reduction of YAP and/or Nrf2 expressions could reduce cell migration, we analyzed this parameter through the wound healing method in Nrf2 silenced, YAP knocked down cells and in cells silenced for both genes (Fig.…”