When it comes to prostate cancer, androgen (AR) and glucocorticoid (GR) receptor signalling play opposing roles: in the prostate, AR functions as an oncogene and GR as a tumour suppressor. Recently, we discovered that the non-steroidal phytochemical compound A (CpdA) is an anti-inflammatory anti-androgen that modulates AR/GR. CpdA suppresses GR transrepression while suppressing AR and preventing GR transactivation. Degradation by proteasomes regulates GR and AR. We discovered that prolonged treatment with the proteasome inhibitor Bortezomib (BZ) resulted in the accumulation of GR and the degradation of AR in prostate cancer (PCa) cells LNCaP, LNCaP-GR, DU145, and PC3. BZ improved CpdA's capacity to suppress AR and increase GR transrepression. Additionally, we discovered that CpdA+BZ differently regulated GR/AR to inhibit PCa cell growth and survival while simultaneously inducing endoplasmic reticulum stress (ERS). The differential regulation of GR-responsive genes by CpdA+BZ is significant (Ikekawa T 2001).
Glucocorticoid-responsive pro-survival genes, such as SGK1, were inhibited by CpdA+BZ, but BZ-induced ERSrelated genes BIP/HSPA5 and CHOP/GADD153 were activated. We demonstrated using ChIP that the effects of CpdA and CpdA+BZ on GR loading on the promoters of SGK1, BIP/HSPA5, and CHOP were responsible for their regulation. In addition, we discovered that AR and GR were widely expressed in advanced PCa from patients who underwent androgen ablation and/or chemotherapy: 56% of these patients' carcinomas exhibited both receptors, whereas the remaining 27% expressed either GR or AR. Overall, our findings support the idea that prostate cancer (PC) may be treated with dual AR/GR targeting, and they point to the great therapeutic potential of the BZ and dual-target steroid receptor modulator CpdA combinations (Kidd PH 2000).
In the past, it has been demonstrated that medicinal mushrooms (basidiomycetes) have significant healthpromoting effects, and current research—which is presented here—is now verifying this and identifying many of the bioactive chemicals in these mushrooms. Large-scale solid substrate and liquid culture fermentation cultivation techniques are also briefly covered (Tsumoo H et al., 1994).
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