https://scholars.lib.ntu.edu.tw/handle/123456789/431149
標題: | Improved effects of honokiol on temozolomide-induced autophagy and apoptosis of drug-sensitive and -tolerant glioma cells | 作者: | Chio C.-C. Chen K.-Y. Chang C.-K. Chuang J.-Y. Liu C.-C. SHING-HWA LIU Chen R.-M. |
關鍵字: | Autophagy and apoptosis; Drug tolerance; Glioma cells; Honokiol; Temozolomide | 公開日期: | 2018 | 出版社: | BioMed Central Ltd. | 卷: | 18 | 期: | 1 | 來源出版物: | BMC Cancer | 摘要: | Background: Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. Methods: TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed. To determine the death mechanisms, caspase-3 activity, DNA fragmentation, apoptotic cells, necrotic cells, cell cycle, and autophagic cells. The glioma cells were pretreated with 3-methyladenine (3-MA) and chloroquine (CLQ), two inhibitors of autophagy, and then exposed to honokiol or TMZ. Results: Exposure of human U87-MG glioma cells to honokiol caused cell death and significantly enhanced TMZ-induced insults. As to the mechanism, combined treatment of human U87-MG cells with honokiol and TMZ induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G1 phase but did not affect cell necrosis. The improved effects of honokiol on TMZ-induced cell insults were further verified in mouse GL261 glioma cells. Moreover, exposure of drug-tolerant human U87-MG-R9 cells to honokiol induced autophagy and consequent apoptosis. Pretreatments with 3-MA and CLQ caused significant attenuations in honokiol- and TMZ-induced cell autophagy and apoptosis in human TMZ-sensitive and -tolerant glioma cells. Conclusions: Taken together, this study demonstrated the improved effects of honokiol with TMZ on autophagy and subsequent apoptosis of drug-sensitive and -tolerant glioma cells. Thus, honokiol has the potential to be a drug candidate for treating human gliomas. ? 2018 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044869266&doi=10.1186%2fs12885-018-4267-z&partnerID=40&md5=78ba2284bb0e3e4e69cf92954615cff8 https://scholars.lib.ntu.edu.tw/handle/123456789/431149 |
ISSN: | 1471-2407 | DOI: | 10.1186/s12885-018-4267-z | SDG/關鍵字: | 3 methyladenine; caspase 3; chloroquine; honokiol; temozolomide; antineoplastic agent; biphenyl derivative; caspase 3; honokiol; lignan; temozolomide; animal cell; antineoplastic activity; apoptosis; Article; autophagy; cancer combination chemotherapy; cancer resistance; cell cycle; cell viability; chemosensitivity; controlled study; DNA fragmentation; drug mechanism; drug potentiation; drug tolerance; enzyme activity; glioma cell; human; human cell; LC50; mouse; nonhuman; apoptosis; autophagy; cell cycle checkpoint; cell survival; drug effect; drug potentiation; drug resistance; glioma; metabolism; tumor cell line; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Biphenyl Compounds; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Drug Synergism; Glioma; Humans; Lignans; Temozolomide |
顯示於: | 毒理學研究所 |
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