论文部分内容阅读
Role of signal transduction pathways activated by stress hormone epinephrine (adrenaline) (1) and methodologies of selectively inhibiting anti-apoptotic signaling pathways in prostate cancer (2) will be discussed.(1) Prostate cancer patients have increased levels of stress and anxiety.Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline, have a lower incidence of prostate cancer;however, the mechanisms underlying stress-prostate cancer interactions are Here, we report that behavioral stress inhibited apoptosis and delayed prostate tumor involution PTEN-deficient prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide.These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway.Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling.(2) The phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway is constitutively activated in a substantial proportion of prostate tumors and is considered a key mechanism supporting progression toward an androgen-independent status, for which no effective therapy is available.To selectively target advanced prostate tumors with a constitutive activated PI3K/Akt pathway, a prostate cancer-specific PI3K inhibitor was generated by coupling the chemically modified form of the quercetin analogue LY294002 (HO-CH2-LY294002) with the peptide Mu-LEHSSKLQ.The result is a water-soluble and latent PI3K inhibitor prodrug, the L-O-CH2-LY294002 that can specifically inhibit PI3K in PSA-secreting prostate cancer cells and induce apoptosis with a potency comparable to that of the original LY294002 compound.