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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 596496, 10 pages
http://dx.doi.org/10.1155/2013/596496
Research Article

Quercetin Induces Mitochondrial Mediated Apoptosis and Protective Autophagy in Human Glioblastoma U373MG Cells

1Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 66 Jejudaehakno, Jeju 690-756, Republic of Korea
2Subtropical Horticulture Research Institute, Jeju National University, Jeju 690-756, Republic of Korea
3Department of Oriental Pathology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong dongdaemun-gu, Seoul 130-701, Republic of Korea

Received 5 August 2013; Revised 16 October 2013; Accepted 28 October 2013

Academic Editor: Tullia Maraldi

Copyright © 2013 Hyeonji Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Quercetin is a dietary flavonoid with known antitumor effects against several types of cancers by promoting apoptotic cell death and inducing cell cycle arrest. However, U373MG malignant glioma cells expressing mutant p53 are resistant to a 24 h quercetin treatment. In this study, the anticancer effect of quercetin was reevaluated in U373MG cells, and quercetin was found to be significantly effective in inhibiting proliferation of U373MG cells in a concentration-dependent manner after 48 and 72 h of incubation. Quercetin induced U373MG cell death through apoptosis, as evidenced by the increased number of cells in the sub-G1 phase, the appearance of fragmented nuclei, decreased mitochondrial membrane potential, proteolytic activation of caspase-3 and caspase-7, an increase in caspase-3 and 9 activities, and degradation of poly(ADP-ribose) polymerase protein. Furthermore, quercetin activated JNK and increased the expression of p53, which translocated to the mitochondria and simultaneously led to the release of cytochrome c from mitochondria to the cytosol. We also found that quercetin induced autophagy. Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in U373MG cells, indicating that quercetin induced protective autopagy in U373MG cells.