title: Autophagic cell death induced by 5-FU in Bax or PUMA deficient human colon cancer cell.
abstract: Autophagy is a membrane process that results in the transporting of cellular contents to lysosomes for degradation. Autophagic cell death is another way of programed cell death called type II PCD, which has complicated connection with apoptosis, both of these two types of cell death play an important role in tumor development. In this study, we investigated chemotherapeutic agent induced cell death pathway in wild type (WT), Bax(-/-) and PUMA(-/-) HCT116 cells. Bax or PUMA deficient cells had similar chemosensitivity to WT cells but were defective in undergoing apoptosis. The results of electron microscopy and GFP-LC3 localization assay showed that autophagy was induced in Bax or PUMA deficient cells but not in WT cells. mTOR activity was decreased in Bax or PUMA deficient cells which further indicated the up-regulation of autophagy. Inhibition of autophagy by 3-Methyladenine (3-MA) decreased the cell death in Bax or PUMA deficient cells. Taken together, these results suggest that autophagic cell death can be used as an alternative cell death pathway in apoptosis defective cells and may bring a new target for cancer therapy.
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Hai-yan
authors: HY
authors: Xiong
authors: Xian-ling
authors: XL
authors: Guo
authors: Xin-xin
authors: XX
authors: Bu
authors: Shan-shan
authors: SS
authors: Zhang
authors: Nan-nan
authors: NN
authors: Ma
authors: Jian-rui
authors: JR
authors: Song
authors: Fei
authors: F
authors: Hu
authors: Shuang-fen
authors: SF
authors: Tao
authors: Kai
authors: K
authors: Sun
authors: Rong
authors: R
authors: Li
authors: Meng-chao
authors: MC
authors: Wu
authors: Li-xin
authors: LX
authors: Wei
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C438378:BBC3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; C025946:3-methyladenine; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D000225:Adenine; D005472:Fluorouracil