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Role of Bax in quercetin-induced apoptosis in human prostate cancer cells.
Biochem Pharmacol. 2008 Jun 15; 75(12):2345-55.BP

Abstract

The aim of this study was to investigate the effect of quercetin, a flavonoid, on the apoptotic pathway in a human prostate cell line (LNCaP). We observed that treatment of cells for 24h with quercetin-induced cell death in a dose-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in quercetin-treated cells. Treatment of LNCaP cells with an apoptosis inducing concentration of quercetin (100 microM) resulted in a rapid decrease in the inhibitory Ser473 phosphorylation of Akt leading to inhibition of its kinase activity. Quercetin treatment (100 microM) also caused a decrease in Ser136 phosphorylation of Bad, which is a downstream target of Akt. Protein interaction assay revealed that during treatment with quercetin, Bcl-xL dissociated from Bax and then associated with Bad. Our results also show that quercetin decreases the Bcl-xL:Bax ratio and increases translocation and multimerization of Bax to the mitochondrial membrane. The translocation is accompanied by cytochrome c release, and procaspases-3, -8 and -9 cleavage and increased poly(ADP-ribose) polymerase (PARP) cleavage. Similar results were observed in human colon cancer HCT116Bax+/+ cell line, but not HCT116Bax-/- cell line. Interestingly, at similar concentrations (100 microM), quercetin treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cell line (PrEC) and rat prostate epithelial cell line (YPEN-1). Our results indicate that the apoptotic processes caused by quercetin are mediated by the dissociation of Bax from Bcl-xL and the activation of caspase families in human prostate cancer cells.

Authors+Show Affiliations

Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. leeyj@upmc.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18455702

Citation

Lee, Dae-Hee, et al. "Role of Bax in Quercetin-induced Apoptosis in Human Prostate Cancer Cells." Biochemical Pharmacology, vol. 75, no. 12, 2008, pp. 2345-55.
Lee DH, Szczepanski M, Lee YJ. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem Pharmacol. 2008;75(12):2345-55.
Lee, D. H., Szczepanski, M., & Lee, Y. J. (2008). Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochemical Pharmacology, 75(12), 2345-55. https://doi.org/10.1016/j.bcp.2008.03.013
Lee DH, Szczepanski M, Lee YJ. Role of Bax in Quercetin-induced Apoptosis in Human Prostate Cancer Cells. Biochem Pharmacol. 2008 Jun 15;75(12):2345-55. PubMed PMID: 18455702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. AU - Lee,Dae-Hee, AU - Szczepanski,Miroslaw, AU - Lee,Yong J, Y1 - 2008/03/29/ PY - 2008/01/21/received PY - 2008/03/20/revised PY - 2008/03/21/accepted PY - 2008/5/6/pubmed PY - 2008/6/17/medline PY - 2008/5/6/entrez SP - 2345 EP - 55 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 75 IS - 12 N2 - The aim of this study was to investigate the effect of quercetin, a flavonoid, on the apoptotic pathway in a human prostate cell line (LNCaP). We observed that treatment of cells for 24h with quercetin-induced cell death in a dose-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in quercetin-treated cells. Treatment of LNCaP cells with an apoptosis inducing concentration of quercetin (100 microM) resulted in a rapid decrease in the inhibitory Ser473 phosphorylation of Akt leading to inhibition of its kinase activity. Quercetin treatment (100 microM) also caused a decrease in Ser136 phosphorylation of Bad, which is a downstream target of Akt. Protein interaction assay revealed that during treatment with quercetin, Bcl-xL dissociated from Bax and then associated with Bad. Our results also show that quercetin decreases the Bcl-xL:Bax ratio and increases translocation and multimerization of Bax to the mitochondrial membrane. The translocation is accompanied by cytochrome c release, and procaspases-3, -8 and -9 cleavage and increased poly(ADP-ribose) polymerase (PARP) cleavage. Similar results were observed in human colon cancer HCT116Bax+/+ cell line, but not HCT116Bax-/- cell line. Interestingly, at similar concentrations (100 microM), quercetin treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cell line (PrEC) and rat prostate epithelial cell line (YPEN-1). Our results indicate that the apoptotic processes caused by quercetin are mediated by the dissociation of Bax from Bcl-xL and the activation of caspase families in human prostate cancer cells. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/18455702/Role_of_Bax_in_quercetin_induced_apoptosis_in_human_prostate_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(08)00194-9 DB - PRIME DP - Unbound Medicine ER -