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Title 

Hypoxia inhibition of camptothecin-induced apoptosis by Bax loss

Authors 

K ParkA S WoubitC D FerminG ReddyT HabtemariamJ W ChungM ParkD W SeolMoonil Kim

Publisher 

Springer Verlag (Germany)

Issue Date 

2012

Citation 

Biologia, vol. 67, no. 3, pp. 616-621

Keywords 

apoptosisBaxcamptothecincolon cancerhypoxia

Abstract 

Tumor cell hypoxia is linked to the resistance of human solid tumors to the various anti-cancer therapies: thus, its exploitation has been considered to be a potential target for cancer treatment. Previously, we demonstrated for the first time that hypoxia inhibits apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) through blocking translocation of Bax, a pro-apoptotic protein, from the cytosol to the mitochondria. Nevertheless, the molecular mechanism coupling hypoxia to resistance for drugs, especially for anti-cancer chemotherapeutics, still remains to be elucidated. Here, we demonstrate that hypoxia attenuates camptothecin (CPT)-induced apoptosis by decreasing the protein levels of Bax, thereby leading to resistance to the drug. DNA damage after exposure to CPT resulted in an increase of p53, and a concomitant up-regulation of p21, regardless of oxygen content. Under normoxic condition, CPT induced expression of p53 and its down-stream target molecule Bax as well, in the presence of increased p21. In contrast, when preexposed to hypoxia, Bax-inducing activity of CPT was completely lost and the Bax level was even decreased, although CPT increased both p53 and p21 as observed under normoxic condition. Our data indicate that hypoxia attenuates apoptosis via Bax. Our data also suggest that hypoxia regulates tumor cell apoptosis differentially, through regulating Bax translocation or through down-regulating Bax levels, depending on death-inducing signals as shown by TRAIL- or CPT-induced apoptosis.

ISSN 

0006-3088

Link 

http://dx.doi.org/10.2478/s11756-012-0037-6

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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