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Biologia




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Volume 67, Issue 3

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Hypoxia inhibition of camptothecin-induced apoptosis by Bax loss

Kyoungsook Park
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
  • BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon, 305-333, Korea
  • School of Engineering, University of Science and Technology (UST), Daejeon, 305-333, Korea
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/ Abdela Woubit
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
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/ Cesar Fermin
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
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/ Gopal Reddy
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
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/ Tsegaye Habtemariam
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
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/ Jin Chung / Minseo Park / Dai-Wu Seol
  • Faculty of Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea
  • Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA
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/ Moonil Kim
  • Department of Pathobiology, College of Veterinary Medicine Nursing & Allied Health (CVMNAH), Tuskegee University, Tuskegee, AL, 36088, USA
  • BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon, 305-333, Korea
  • School of Engineering, University of Science and Technology (UST), Daejeon, 305-333, Korea
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Published Online: 2012-04-18 | DOI: https://doi.org/10.2478/s11756-012-0037-6

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.

Keywords: Bax; camptothecin; apoptosis; hypoxia; colon cancer

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About the article

Published Online: 2012-04-18

Published in Print: 2012-06-01


Citation Information: Biologia, Volume 67, Issue 3, Pages 616–621, ISSN (Online) 1336-9563, ISSN (Print) 0006-3088, DOI: https://doi.org/10.2478/s11756-012-0037-6.

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© 2012 Slovak Academy of Sciences. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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