Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3)

Abstract

Progression of prostate cancer is facilitated by growth factors that activate critical signaling cascades thereby promote prostate cancer cell growth, survival, and migration. To investigate the effect of quercetin on insulin-like growth factor signaling and apoptosis in androgen independent prostate cancer cells (PC-3), IGF-IR, PI-3K, p-Akt, Akt, cyclin D1, Bad, cytochrome c, PARP, caspases-9 and 10 protein levels were assessed by western blot analysis. Mitochondrial membrane potency was detected by rhodamine-123 staining. Quercetin induced caspase-3 activity assay was performed for activation of apoptosis. Further, RT-PCR was also performed for Bad, IGF-I, II, IR, and IGFBP-3 mRNA expression. Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells. IGF-IRβ, PI3K, p-Akt, and cyclin D1 protein expression and mRNA levels of IGF-I, II and IGF-IR were decreased significantly. Further, treatment with PI3K inhibitor (LY294002) and quercetin showed decreased p-Akt levels. Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells. This study suggests that quercetin decreases the survival of androgen independent prostate cancer cells by modulating the expression of insulin-like growth factors (IGF) system components, signaling molecules and induces apoptosis, which could be very useful for the androgen independent prostate cancer treatment.

Expression of prostate stem cell antigen is downregulated during flavonoid-induced cytotoxicity in prostate cancer cells

“…Analogous to previous studies in human prostate cancer cells (24,(28)(29)(30), the present study demonstrated that genistein, luteolin and quercetin induced apoptosis in DU145 cells. Thus, genistein, luteolin and quercetin may inhibit the growth of prostate cancer cells through the induction of cell cycle arrest and apoptosis.…”

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

“…Apoptosis can be triggered in a cell through either the extrinsic pathway or the intrinsic pathway (Elmore 2007;Putcha et al 2002). The extrinsic pathway is initiated through the stimulation of the transmembrane death receptors, such as the Fas receptors (Heimlich and Cidlowski 2006;Senthilkumar et al 2010). In contrast, the intrinsic pathway is initiated through the release of signal factors by mitochondria within the cell.…”

Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC‐3)

“…Quercetin significantly decreased the b-catenin protein expression. Our previous report showed that quercetin inhibited the phosphorylation of Akt, 46 which may consequently inhibit the phosphorylation of GSK-3. Here, we provide evidence suggests that quercetin is a potent sensitizer by downregulating uPA, uPAR, EGF, EGF-R mRNA and NF-kB, b-catenin, Ras Raf signalling molecules thereby decreasing cell survival, proliferation, migration and invasion of PC-3 cells.…”