Chen C.-M.Syu J.-P.Way T.-D.Huang L.-J.Kuo S.-C.CHUNG-TIEN LINLin C.-L.2020-01-072020-01-0720151107-3756https://scholars.lib.ntu.edu.tw/handle/123456789/446386Glioblastoma multiforme (GBM) is the most fatal form of human brain cancer. Although temozolomide (TMZ), an oral alkylating chemotherapeutic agent, improves the survival rate, the prognosis of patients with GBM remains poor. Naturally occurring carbazole alkaloids isolated from curry leaves (Murraya koenigii Spreng.) have been shown to possess a wide range of anticancer properties. However, the effects of carbazole derivatives on glioblastoma cells remain poorly understood. In the present study, anti-glioblastoma profiles of a series of synthetic carbazole derivatives were evaluated in vitro. The most promising derivative in this series was BC3EE2,9B, which showed significant anti-proliferative effects in GBM8401 and GBM8901 cells. BC3EE2,9B also triggered cell-cycle arrest, most prominently at the G1 stage, and suppressed glioblastoma cell invasion and migration. Furthermore, BC3EE2,9B induced autophagy-mediated cell death and synergistically sensitized GBM cells to TMZ cytotoxicity. The possible mechanism underlying BC3EE2,9B-induced autophagy may involve activation of adenosine monophosphate-activated protein kinase and the attenuation of the Akt and mammalian target of the rapamycin downstream signaling pathway. Taken together, the present results provide molecular evidence for the mode of action governing the ability of BC3EE2,9B to sensitize drug-resistant glioblastoma cells to the chemotherapeutic agent TMZ. ? Spandidos Publications 2015.Akt; Autophagy; Carbazole; Glioblastoma; Temozolomide[SDGs]SDG3antineoplastic agent; bc 3ee 29b; carbazole derivative; hydroxymethylglutaryl coenzyme A reductase kinase; mammalian target of rapamycin; protein kinase B; temozolomide; unclassified drug; antineoplastic agent; carbazole; carbazole derivative; dacarbazine; protein kinase B; temozolomide; antineoplastic activity; antiproliferative activity; Article; autophagy; cancer inhibition; chemosensitization; controlled study; drug mechanism; drug potentiation; enzyme activation; G1 phase cell cycle checkpoint; glioblastoma; glioblastoma cell line; human; human cell; in vitro study; metastasis inhibition; priority journal; signal transduction; tumor invasion; upregulation; analogs and derivatives; autophagy; Brain Neoplasms; cell cycle checkpoint; cell cycle G1 phase; cell motion; cell proliferation; drug effects; drug potentiation; drug resistance; genetics; glioblastoma; pathology; tumor cell line; Antineoplastic Agents; Autophagy; Brain Neoplasms; Carbazoles; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dacarbazine; Drug Resistance, Neoplasm; Drug Synergism; G1 Phase; Glioblastoma; Humans; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt; Signal Transduction; Up-Regulationjournal article10.3892/ijmm.2015.23322-s2.0-84945340336https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84945340336&doi=10.3892%2fijmm.2015.2332&partnerID=40&md5=7a99a20d0ee169a6fbe41c4484d0b3fc