Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2',4'-dihydroxy-6'-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s).
However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.
IL-6 signals through Janus kinase, signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase and is also able to induce androgen receptor (AR)-mediated gene activation in prostate cancer, which is an important process in prostate cancer androgen-independent progression.
In addition to the activation of oncogenes c-MYC and STAT3 in tumor cells, a number of cytokines and growth factors, such as IL1β, IL6 and SPP1 (osteopontin, a key biomarker for PCa), were upregulated in NFATc1-induced PCa, establishing a tumorigenic microenvironment involving both NFATc1 positive and negative cells for prostate tumorigenesis.
In addition, suppression of ZIC5 or PDGFD expression decreased levels of phosphorylated focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) which are associated with PCa and CRC aggressiveness.
In the present study, we examined that betulinic acid (BA), a triterpene from the bark of white birch, had the inhibitory effects on hypoxia-mediated activation of STAT3 in androgen independent human prostate cancer PC-3 cells.
In this study, we demonstrate that interleukin 6 induces both WASF3 expression and phosphoactivation in breast and prostate cancer cell lines through the JAK2/STAT3 pathway in two different ways.
In this study, we examined the effect of HDL and S1P on Stat3 activation in prostate cancer cells and the involvement of S1P receptors in this process in three prostate cancer cell lines (PC-3, LNCaP, and DU145).
Interleukin-6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression.
Mechanistic studies focusing on transcription factors involved in apoptotic and survival pathways revealed that B2G2 significantly inhibits NF-κB and activator protein1 (AP1) transcriptional activity and nuclear translocation of signal transducer and activator of transcription3 (Stat3) in PCa cell lines, irrespective of their functional androgen receptor status.
Mitogen-activated Protein Kinase 8 (MAPK8), Interleukin 6 (IL6), Vascular Endothelial Growth Factor A (VEGFA), Signal Transducer and Activator of Transcription 3 (STAT3), Jun Proto-Oncogene (JUN), C-X-C Motif Chemokine Ligand 8 (CXCL8), Interleukin-1 Beta (IL1B), Matrix Metalloproteinase-9 (MMP9), C-C Motif Chemokine Ligand 2 (CCL2), RELA Proto-Oncogene (RELA), and CAMP Responsive Element Binding Protein 1 (CREB1) were identified as key targets of HDW in the treatment of PCa.
Moreover, in malignant cells harboring constitutively-active Stat3, including human prostate cancer DU145 cells and v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), resveratrol treatment represses Stat3-regulated cyclin D1 as well as Bcl-xL and Mcl-1 genes, suggesting that the antitumor cell activity of resveratrol is in part due to the blockade of Stat3-mediated dysregulation of growth and survival pathways.
Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers).
Our results demonstrate that expression of wt p53 but not mutant p53 significantly reduced tyrosine phosphorylation of Stat3 and inhibited Stat3 DNA binding activity in both DU145 and Tsu prostate cancer cell lines that express constitutively active Stat3.
Our results indicate that the most primitive cells in prostate cancer require pSTAT3 for survival, rationalizing STAT3 as a therapeutic target to treat advanced prostate cancer.
Overall, these results suggest that STAT3 inhibition is a rational therapeutic approach for ENZ<sup>R</sup> prostate cancer, and could be valuable in CRPC in combination with ENZ.
Paraffin-embedded specimens from 92 patients with clinically localized prostate cancer who underwent radical prostatectomy without neoadjuvant treatment were analyzed by immunohistochemistry using two antibodies: anti-phospho-specific STAT3 (p-STAT3) antibody, which recognized only activated STAT3, and anti-total STAT3 antibody, which recognized both activated and inactivated STAT3.