title: Contribution of autophagic cell death to p53-dependent cell death in human glioblastoma cell line SF126.
abstract: Apoptosis and autophagic cell death are programmed cell deaths that are involved in cell survival, growth, development and carcinogenesis. p53, the most extensively studied tumor suppressor, regulates apoptosis and autophagy by transactivating its downstream genes. It also stimulates the mitochondrial apoptotic pathway and inhibits autophagy in a transactivation-independent manner. However, the contribution of apoptosis and autophagic cell death to p53-dependent cell death is unclear. Using wild-type (WT) and mutant (MT) p53 inducible cell lines in TP53-null SF126 glioblastoma cells, we examined the apoptosis and autophagic cell death induced by p53. WT p53 expression in SF126 cells induced apoptosis and autophagy, and reduced the cell number. An autophagy inhibitor reduced autophagy, increased the S-phase fraction, and attenuated the inhibition of cell proliferation induced by WT p53. Pan-caspase inhibitor reduced apoptosis but showed weaker inhibition of cell proliferation than the autophagy inhibitor. We concluded that p53-dependent cell death in SF126 cells comprises caspase-dependent and caspase-independent apoptosis and autophagic cell death, and the induction of autophagy as well as apoptosis could be a new strategy to treat some type of WT p53-retaining tumors.
authors.affiliation: Department of Clinical Oncology, Research Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Okada
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Yasuda
authors.forename: Gou
authors.initials: G
authors.lastname: Watanabe
authors.forename: Hiroo
authors.initials: H
authors.lastname: Imai
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020169:Caspases