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. 1. Introduction Glioblastoma is the most common type of primary brain tumor in adults and the most lethal and least successfully treated tumor. The low absolute incidence combined with high morbidity, poor response rate, and short survival time poses practical problems for clinical trial execution [1]. Less than 30% of patients suffering from this devastating disease survive 12–15 months, even after receiving multimodal treatments such as surgical resection, combined chemotherapy and radiotherapy, and adjuvant chemotherapy [2]. These observations underscore the need for alternative therapies to prevent and effectively treat glioblastoma. Quercetin is an antioxidative flavonoid ubiquitously distributed in plants. Its anticancer effects have been attributed to antioxidative activity, inhibition of enzymes activating carcinogens, modification of signal transduction pathways, and interactions with receptors and other proteins [3]. Quercetin is an anticancer agent in many cancer models [4–12]. Several studies have reported that quercetin increases the efficacy of glioblastoma treatment by suppressing the PI-3-kinase-Akt pathway [13], inducing apoptosis by reducing X-linked inhibitor of apoptosis protein (XIAP) [14], blocking signal transducer and activator of transcription 3 (STAT3) [15],
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