You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
In vitro influence of Amitriptyline on glioma cell oxygen<br />
comsumption and viability using oxygen electrode assay<br />
and Vi-Cell TM automated trypan blue dye exclusion assay<br />
S. Higgins and G. J. Pilkington<br />
Cellular & Molecular Neuro-Oncology Group, School of Pharmacy & Biomedical Sciences,<br />
Institute of Biomedical & Biomolecular Sciences, University of Portsmouth, White Swan<br />
Road, Portsmouth PO1 2DT<br />
Introduction: We have previously reported that the tricyclic antidepressant<br />
Clomipramine exerts a pro-apoptotic effect on neoplastic glial cells in vitro. This<br />
effect is mediated via the mitochondria where cytochrome C liberation and activation<br />
of caspases precedes apoptosis. There is increasing evidence in our laboratories,<br />
however, that additional tricyclics - Amitriptyline and its metabolic product,<br />
Nortriptyline - may play a similar role.<br />
Methods: The influence of Amitriptyline & Nortriptyline at a range of concentrations<br />
on oxygen consumption in a) non-neoplastic human astrocytes (CC-2565 Cambrex<br />
Biosciences), b) a short-term cultured of biopsy-derived human glioblastoma<br />
multiforme (UPMC) and c) an established human anaplastic astrocytoma cell line<br />
(IPSB-18) was studied using a Hansatech, Clark-type Oxytherm TM & Oxygraph TM<br />
multiple series oxygen electrode apparatus. Cell viability was then studied under<br />
similar experimental conditions using the trypan blue dye exclusion test in a<br />
Vi-Cell TM XR Cell viability analyzer.<br />
Results: The influence of Amitriptyline was more pronounced than that of its<br />
metabolic product, Nortriptyline, both in reduction of oxygen consumption and cell<br />
viability and both were concentration-dependent. The order of the level of sensitivity<br />
84p13<br />
between different type of cell culture to both agents was UPMC>IPSB-18>CC-2565.<br />
Discussion: The high level of resistance of CC-2565 supports a specific anti-neoplastic<br />
role for the tricyclics in the management of primary malignant brain tumours.<br />
However, although Amitriptyline crosses the blood-brain barrier and specifically<br />
kills tumour cells, the lower efficacy of Nortriptyline (which results from conversion<br />
of Amitryptyline in the liver) may suggest that local administration of Amitriptyline<br />
to the brain may confer better therapeutic potential.
Change language