The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells
Article first published online: 20 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 29, Issue 4, pages 428–439, April 2014
How to Cite
Liu, K.-C., Yen, C.-Y., Wu, R. S.-C., Yang, J.-S., Lu, H.-F., Lu, K.-W., Lo, C., Chen, H.-Y., Tang, N.-Y., Wu, C.-C. and Chung, J.-G. (2014), The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells. Environ. Toxicol., 29: 428–439. doi: 10.1002/tox.21769
- Issue published online: 6 MAR 2014
- Article first published online: 20 MAR 2012
- Manuscript Accepted: 1 FEB 2012
- Manuscript Revised: 29 JAN 2012
- Manuscript Received: 10 NOV 2011
- China Medical University. Grant Number: CMU100-S-14
- National Science Council, Republic of China (Taiwan). Grant Number: NSC 96-2815-C-039-047-B
- ER stress;
- prostate cancer PC-3 cells
Prostate cancer has its highest incidence and is becoming a major concern. Many studies have shown that traditional Chinese medicine exhibited antitumor responses. Quercetin, a natural polyphenolic compound, has been shown to induce apoptosis in many human cancer cell lines. Although numerous evidences show multiple possible signaling pathways of quercetin in apoptosis, there is no report to address the role of endoplasmic reticulum (ER) stress in quercetin-induced apoptosis in PC-3 cells. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human prostate cancer PC-3 cells. Cells were treated with quercetin for 24 and 48 h and at various doses (50–200 μM), and cell morphology and viability decreased significantly in dose-dependent manners. Flow cytometric assay indicated that quercetin at 150 μM caused G0/G1 phase arrest (31.4–49.7%) and sub-G1 phase cells (19.77%) for 36 h treatment and this effect is a time-dependent manner. Western blotting analysis indicated that quercetin induces the G0/G1 phase arrest via decreasing the levels of CDK2, cyclins E, and D proteins. Quercetin also stimulated the protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress. Furthermore, PC-3 cells after incubation with quercetin for 48 h showed an apoptotic cell death and DNA damage which are confirmed by DAPI and Comet assays, leading to decrease the antiapoptotic Bcl-2 protein and level of ΔΨm, and increase the proapoptotic Bax protein and the activations of caspase-3, -8, and -9. Moreover, quercetin promoted the trafficking of AIF protein released from mitochondria to nuclei. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade through mitochondrial pathway and ER stress in PC-3 cells. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 428–439, 2014.