title: Induction of survivin inhibition, G₂/M cell cycle arrest and autophagic on cell death in human malignant glioblastoma cells.
abstract: Chemotherapy efficacy is limited by intrinsic and acquired resistance in glioblastoma (GBM); hence, novel tactics are crucial. Survivin has been demonstrated as a key resistant factor in GBM because of its function in inhibiting apoptosis, regulating autophagy, and in promoting G₂/M cell cycle transition. Parthenolide has been reported to be an effective antitumor agent in a variety of tumor cells and decreases survivin level in leukemia cells. But the effect of parthenolide on survivin and the cell death process in GBM is still unknown. The aim of this study was to examine whether parthenolide had the potential to inhibit cell proliferation in the GBM cell line U373. The parthenolide-induced effects in relation to survivin suppression and cell death were further investigated. Our results showed that parthenolide substantially inhibited cell viability with IC₅₀ values of approximate 16 μM. Treatment with parthenolide at the dose of 16 μM led to considerable downregulation of survivin, G₂/M cell cycle arrest and Chk2 upregulation in cells. Parthenolide induced apoptosis in only a few cells and a slight increase in activated caspases 3 levels. By contrast, parthenolide induced a significant increase of intracellular autophagosomes and the expression of autophagy related proteins, including ULK1 and LC3 I/LC3 II, in the treated cells. These results suggested that parthenolide induced survivin inhibition, G₂/M cell cycle arrest, and triggered cell death through autophagic cell death in the GBM cell line.
authors: Department of Nursing, National Quemoy University, Kinmen 89250, Taiwan, Republic of China.
authors: Tswen-Kei
authors: TK
authors: Tang
authors: Department of Radiation Oncology, Hsinchu Mackay Memorial Hospital, Hsinchu 30015, Taiwan, Republic of China.
authors: Shih-Che
authors: SC
authors: Chiu
authors: Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
authors: Chia-Wen
authors: CW
authors: Lin
authors: Department of Biomedical Engineering, Yuanpei University, HsinChu 30015, Taiwan, Republic of China.
authors: Mei-Ju
authors: MJ
authors: Su
authors: Department of Biomedical Engineering, Yuanpei University, HsinChu 30015, Taiwan, Republic of China.
authors: May-Hua
authors: MH
authors: Liao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012717:Sesquiterpenes; D000077022:Survivin; C002669:parthenolide