title: Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells.
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.
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 66 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Hyeonji
authors.initials: H
authors.lastname: Kim
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 66 Jejudaehakno, Jeju 690-756, Republic of Korea ; Subtropical Horticulture Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Jeong Yong
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Oriental Pathology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 66 Jejudaehakno, Jeju 690-756, Republic of Korea ; Subtropical Horticulture Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Somi Kim
authors.initials: SK
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D009363:Neoplasm Proteins; D002738:Chloroquine; D011794:Quercetin