Autophagic cell death induced by 5-FU in Bax or PUMA deficient human colon cancer cell.
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.
Xiong
Hai-yan
HY
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Guo
Xian-ling
XL
Bu
Xin-xin
XX
Zhang
Shan-shan
SS
Ma
Nan-nan
NN
Song
Jian-rui
JR
Hu
Fei
F
Tao
Shuang-fen
SF
Sun
Kai
K
Li
Rong
R
Wu
Meng-chao
MC
Wei
Li-xin
LX
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
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