Quercetin is a dietary flavonoid with known antitumor effects against several types of cancers by promoting apoptotic cell death and inducing cell cycle arrest. 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 usually the most common type of main brain tumor in adults and the most lethal and least successfully treated tumor. The low complete incidence combined with high morbidity, poor response rate, and short survival time positions practical problems for clinical trial performance [1]. Less than 30% of patients suffering from this devastating disease survive 12C15 months, even after receiving multimodal treatments such as surgical resection, combined chemotherapy and radiotherapy, and adjuvant chemotherapy [2]. These observations underscore the need for option therapies to prevent and effectively treat glioblastoma. Quercetin is usually an antioxidative Omecamtiv mecarbil flavonoid ubiquitously distributed in plants. Its anticancer effects have been attributed to antioxidative activity, inhibition of enzymes activating carcinogens, changes of transmission transduction pathways, and interactions with receptors and other proteins [3]. Quercetin is usually an anticancer agent in many malignancy models [4C12]. Several studies have reported that quercetin increases the efficacy of glioblastoma treatment by suppressing the Omecamtiv mecarbil PI-3-kinase-Akt pathway [13], inducing apoptosis by reducing X-linked inhibitor of apoptosis protein (XIAP) [14], blocking transmission transducer and Omecamtiv mecarbil activator of transcription 3 (STAT3) [15], arresting cells at the G2 checkpoint of the cell cycle, and decreasing the mitotic index in glioma cells [16]. Such effects of quercetin in glioblastoma cells seem to be dependent on cell type because HGFR combined application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and quercetin strongly reduces viability of U87MG, U251, A172, and LN229 glioma cells but does not work out to reduce the viability of U373MG cells [17]. The cause of U373MG cell resistance to quercetin-TRAIL-mediated apoptosis is usually not fully comprehended. Inactivating p53 is usually not important in quercetin-TRAIL-mediated apoptosis, as both sensitive U251 and the completely resistant U373MG cells have p53 mutations. Apoptosis is usually programmed cell death mediated by caspases, which are cysteine proteases that cleave target proteins at aspartic acid. p53 is usually a transcription factor that induces the manifestation of proapoptotic genes [18, 19], and activating apoptosis is usually an important mechanism in p53-induced tumor suppression. Mitochondrial localization of mutant p53 and evidence connecting p53 transcription-independent or mitochondria-targeted apoptosis has received considerable attention. A portion of p53 translocates to mitochondria prior to changes in the mitochondrial membrane potential, cytochrome c release, and activation of caspases [20C22]. A previous study suggested that cellular cross-talk may occur between mitochondrial and nuclear p53. Heyne et al. [23] suggested that mutant p53 exists as a monomeric protein in mitochondria, and Tang et al. [24] exhibited that mutant p53 translocates to mitochondria in UVB-irradiated murine skin carcinoma cells. Mahyar-Roemer et al. [25] suggested that mutant p53 is usually present in mitochondria impartial of apoptotic signals. Mihara et al. [26] reported that p53 binds to Bcl-xL Omecamtiv mecarbil via its DNA-binding domain name and that mutant p53 R273H cannot hole Bcl-xL and is usually therefore unable to activate the direct mitochondrial pathway of apoptosis despite being localized in or at the mitochondria. However, mutant p53 can also induce apoptosis through a transcription-independent pathway, in which wild-type p53 and p53 mutants are transiently located to the mitochondria with changes in the mitochondrial membrane potential [27]. Furthermore, a few such transcriptionally impaired p53 mutants (at the.g., the structural mutant R175H and the DNA contact mutants R273H and C277F) hole Bak in vitro, and this is usually correlated with their ability to oligomerize Bak and induce cytochrome c release from isolated mitochondria [28]. We wondered whether mutant p53 R273H affects mitochondrial functions in human glioma blastoma cells. Here, we resolved the question of whether autophagy is usually intimately linked with apoptosis induced by quercetin in U373MG cells. Autophagy is usually an evolutionarily conserved and genetically programmed process that degrades long-lived cellular proteins and organelles. The role of autophagy in malignancy is usually quite complicated and controversial. Autophagy is usually thought to be tumor suppressive during malignancy development but to contribute to tumor cell survival during malignancy progression [29]. Alternatively, autophagy prevents tumor cells from declining by inhibiting apoptosis during nutritional deprivation, and the cells.