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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Xiong HY,Guo XL,Bu XX,Zhang SS,Ma NN,Song JR,Hu F,Tao SF,Sun K,Li R,Wu MC,Wei LX

doi

10.1016/j.canlet.2009.06.039

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

68-74

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(09)00448-0

journal_volume

288

pub_type

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