Edit this page in Wiki Genes or see Wiki Gene.
Mechanisms of cytotoxicity induced by horseradish peroxidase/ indole-3-acetic acid gene therapy. Paper-9336910. Similar effects were observed when the cells were incubated with the apoptotic agent cisplatin. Paper-9336910.
To date, the chemical agents and the cellular targets involved in HRP/IAA-mediated toxicity have not been identified.
In the present work, some of the molecular and morphological features of the cells treated with HRP/IAA gene therapy were analysed.
The cytotoxic potential of HRP/IAA GDEPT and the induction of a bystander effect were demonstrated in vitro under normoxic as well as hypoxic tumour conditions.
The effect of HRP/IAA treatment on cell cycle progression was also investigated, and a rapid cytostatic effect, equally affecting all phases of the division cycle, was observed.
We have previously proposed the horseradish peroxidase (HRP) and the non-toxic plant hormone indole-3-acetic acid (IAA) as a novel system for gene-directed enzyme/prodrug therapy (GDEPT). Paper-9336910.
Human T24 bladder carcinoma cells transiently transfected with the HRP cDNA and exposed to the prodrug IAA showed chromatin condensation, formation of apoptotic bodies, DNA fragmentation, and Annexin V binding. Paper-9336910.
However, very little degradation of one of the downstream targets of caspase-3, PARP, could be detected, and apoptosis alone did not appear to account for the killing levels measured with a clonogenic assay. Paper-9336910.
Caspases appeared to be involved as effectors in HRP/IAA-mediated apoptosis, since treatment with a general caspase inhibitor decreased the fraction of cells with micronuclei (MN) by 30%, with fragmented DNA by 50%, and with condensed chromatin by 60%.
Important links !
iHOP - Information Hyperlinked over Proteins .
Concept & Implementation by Robert Hoffmann.