Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer

Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

“…In addition to the involvement of death inhibitors, such as c-FLIP, several studies indicate constitutively active AKT as an important regulator of differential sensitivity to TRAIL (Chen et al, 2001;Falschlehner et al, 2007). LNCaP cells express highest level of constitutive active AKT, which has been thought to be directly related to their TRAIL resistance.…”

Inhibition of Akt signaling by the lignan matairesinol sensitizes prostate cancer cells to TRAIL-induced apoptosis

“…Instead, our data show that MAT enhances TRAIL-induced Bid cleavage in androgen-deprived LNCaP cells. According to Nesterov et al (2001) and Chen et al (2001), Akt mediates TRAIL-resistance of LNCaP cells, which appears to function through inhibition of Bid cleavage. A recent study by Aslan et al (2009), describes an intriguing link between Akt activity and the proapoptotic actions of Bid in response to TRAIL treatment.…”

“…Treatment with MAT rapidly decreased Akt phosphorylation in both androgendeprived and androgen-stimulated LNCaP cells, indicating a possible mechanism for MAT in the sensitization to TRAIL-induced apoptosis. Inhibition of the PI3K with the small molecule inhibitor LY294002 also results in sensitization LNCaP cells to TRAIL-induced apoptosis (data not shown, Chen et al, 2001). To verify the involvement of the Akt pathway, we transfected LNCaP cells with mock-GFP or constitutively active Akt-GFP (ca-Akt-GFP), and assayed the cells for MAT-mediated sensitization to TRAIL.…”

Integrins as a distinct subtype of dependence receptors

“…94 The activation of MAPKs has been linked to integrin-dependent survival in a number of cases. 40,51,57,67,95 Nevertheless, the activation of PI3K/Akt may be more important at regulating cell viability in the presence of unligated integrins, since constitutively active Akt prevents apoptosis induced via death receptors [96][97][98][99][100] or active forms of caspase 8. 101 It is possible that Akt may phosphorylate a peptide loop on caspase 8 proximal to the catalytic site.…”