R progression from non-tumor parenchyma and Benign Prostatic Hyperplasia (BPH) to tumor illness. On the other hand, nuclear HO-1 staining was stronger within the tumors when in comparison with non-malignant tissues and BPH, suggesting a role in tumor transformation. Other authors have reported a correlation between higher nuclear HO-1 expression with poorer all round survival [68]. In addition, Vazquez et al. ALDH3 custom synthesis demonstrated that in vitro pharmacological therapy with hemin of androgen-sensitive (LNCaP) and androgen-insensitive (PC3) prostate cancer cell lines induced HO-1 overexpression and its nuclear translocation in each tumor subtypes [67]. In addition, hemin-induced HO-1 expression reduced PCa cell proliferation, cell migration and GPR139 web invasion processes also as pro-angiogenic genes expression. In accordance together with the latter locating, HO-1 overexpression repressed the transcriptional activity of NF-kB, a TF involved in inflammation and angiogenesis. Moreover, hemin therapy decreased in vivo neovascularization and tumor development of HO-1-overexpressing PCa xenograft model. Notably, nuclear HO-1 was observed in these tumor xenografts. Within this context, the expression and activity of MMP9, a downstream target of NF-kB in addition to a well-known player in PCa spread, was also downregulated. All these final results demonstrate that HO-1 plays an antitumor part in PCa [69,70]. Connected for the nuclear HO-1 role, the identical authors demonstrated that in testosterone-stimulated LNCaP cells, HO-1 connected together with the proximal area promoter of MMP9, thus modulating its gene expression, too as to uPA and PSA gene promoters [71]. Furthermore, they showed that HO-1 bind to STAT3 retaining it into the cytoplasm, thus impairing its binding for the androgen receptor and STAT3/AR nuclear translocation, as a result leading to a reduced induction of STAT3 target genes [71]. In addition, Dennery et al. demonstrated constitutive nuclear expression of a truncated (28 kDa) kind of HO-1 in LNCaP prostate cancer cell line [23]. The authors showed proof that the nuclear 28 kDa HO-1 co-immunoprecipitates with Nrf2, despite the fact that this Nrf2 is just not phosphorylated at Ser40 , which can be a posttranslational modification thatAntioxidants 2021, 10,7 ofmodulates Nrf2 activity. As an alternative, the authors demonstrated that nuclear HO-1 stabilize Nrf2, hence regulating the transcription of specific downstream antioxidants and metabolic genes [23]. With regard to how HO-1 leaves the sER membrane in PCa, cathepsin B expression in human PCa tissues was reported [72]. Even so, no considerable variations on calpain-1 and -2 expression in tumor versus typical samples have been identified [73]. Whether a few of these enzymes as well as SPP are involved in the HO-1 truncation in these tumor cells remains to become demonstrated. Interestingly, inside a proteomic profiling of HO-1-interacting proteins from HO-1-overexpressed PC3 cells, an enrichment inside the proteins linked with DNA- and chromatin-related processes and with RNA metabolism was reported [74]. Nonetheless, the function of HO-1, and specifically t-HO-1, in such nuclear cellular processes should be completely studied. To elucidate the molecular mechanism of nuclear HO-1 in PCa, Birrane et al. evaluated the impact of smoking medium (SM), which increases the danger for prostate cancer, on nuclear HO-1 translocation and VEGF secretion. They demonstrated that SM induced nuclear HO-1, which mediated VEGF secretion, therefore contributing to angiogenesis. Having said that, it is fascinating to note that the authors have made use of a D.