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Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-kappaB activity.
- Source :
- British Journal of Cancer; 9/15/2003, Vol. 89 Issue 6, p1108-1115, 8p
- Publication Year :
- 2003
-
Abstract
- In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities in the molecular events following Fas and TNF-alpha receptor engagement, we report that U937 cells, genetically engineered to constitutively produce hGH, were made more sensitive to TNF-alpha-induced apoptosis than parental cells. This was due to overproduction of the antioxidant glutathione, which decreased the nuclear factor (NF)-kappaB activity known to control the expression of survival genes. These findings were confirmed in vivo, in nude mice bearing U937 tumours coinjected with recombinant hGH and the NF-kappaB -inducing anticancer drug daunorubicin, to avoid the in vivo toxicity of TNF-alpha. This study therefore highlights one of the various properties of hGH that may have potential clinical implications. [ABSTRACT FROM AUTHOR]
- Subjects :
- GROWTH factors
GLUTATHIONE
APOPTOSIS
LEUKEMIA
NF-kappa B
THERAPEUTICS
TUMOR prevention
ANIMAL experimentation
ANTIGENS
ANTINEOPLASTIC antibiotics
BIOCHEMISTRY
CELLULAR signal transduction
COMPARATIVE studies
DAUNOMYCIN
ELECTROPHORESIS
GENES
GENETIC techniques
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
MICE
RECOMBINANT proteins
RESEARCH
SURVIVAL
TRANSFERASES
TUMOR necrosis factors
TUMORS
DNA-binding proteins
EVALUATION research
HUMAN growth hormone
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 89
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 10800475
- Full Text :
- https://doi.org/10.1038/sj.bjc.6601223