TY - JOUR
T1 - Might telomerase enzyme be a possible target for trans-Pt(II) complexes?
AU - Colangelo, Donato
AU - Ghiglia, Anna Lisa
AU - Viano, Ilario
AU - Mahboobi, Homa
AU - Ghezzi, Anna Rita
AU - Cassino, Claudio
AU - Osella, Domenico
N1 - Funding Information:
This work was financially supported by MIUR (Roma) within PRIN2001 project. We are indebted to Johnson and Matthey (Reading, UK) for a generous loan of K 2 PtCl 4 . AR.G. Thanks CIRCMSB (Bari) for research fellowship. This research was carried out in the frame of the European Cooperation Cost D20 action (Metal compounds in the treatment of cancer and viral diseases) and Cost B16 action (Multidrug resistance reversal).
PY - 2004/1
Y1 - 2004/1
N2 - Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric DNA (TTAGGG) repeats. Previously, we have studied the effect on telomerase enzyme of several cis-platinum(II) complexes bearing aromatic amines as bulky carrier groups. All these complexes possess cis-geometry, according to the Cleare and Hoschele's rule. Since recent reports have dealt with the anti-cancer activity of trans-platinum compounds, in this study we have investigated the Farrell's prototypical trans-[Pt(Cl)2(pyridine) 2], hereafter called trans-PtPy, in order to understand whether it may possess any anti-telomerase activity. The trans-PtPy has low water solubility and requires dimethyl sulfoxide (DMSO) as co-solvent, thus making the biological tests problematic. The effect of trans-PtPy on MCF-7 cell line concerning log-term telomerase inhibition, telomerase-related gene expression, viability, and apoptosis was evaluated. In a cell-free biochemical assay, trans-PtPy showed significant and dose-dependent inhibition of semi-purified telomerase. The bulk of data indicate that trans-PtPy acts as a non-properly selective anti-proliferative agent, although it shows an initial telomerase inhibitory effect. Telomere length reduction seems not to be the main mechanism causing the observed cell apoptosis. For comparison purpose, results on cis-[Pt(Cl)2(pyridine)2], hereafter cis-PtPy, are reported.
AB - Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric DNA (TTAGGG) repeats. Previously, we have studied the effect on telomerase enzyme of several cis-platinum(II) complexes bearing aromatic amines as bulky carrier groups. All these complexes possess cis-geometry, according to the Cleare and Hoschele's rule. Since recent reports have dealt with the anti-cancer activity of trans-platinum compounds, in this study we have investigated the Farrell's prototypical trans-[Pt(Cl)2(pyridine) 2], hereafter called trans-PtPy, in order to understand whether it may possess any anti-telomerase activity. The trans-PtPy has low water solubility and requires dimethyl sulfoxide (DMSO) as co-solvent, thus making the biological tests problematic. The effect of trans-PtPy on MCF-7 cell line concerning log-term telomerase inhibition, telomerase-related gene expression, viability, and apoptosis was evaluated. In a cell-free biochemical assay, trans-PtPy showed significant and dose-dependent inhibition of semi-purified telomerase. The bulk of data indicate that trans-PtPy acts as a non-properly selective anti-proliferative agent, although it shows an initial telomerase inhibitory effect. Telomere length reduction seems not to be the main mechanism causing the observed cell apoptosis. For comparison purpose, results on cis-[Pt(Cl)2(pyridine)2], hereafter cis-PtPy, are reported.
KW - Anti-tumor chemotherapy
KW - Platinum complexes
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=0344687285&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2003.08.009
DO - 10.1016/j.jinorgbio.2003.08.009
M3 - Article
SN - 0162-0134
VL - 98
SP - 61
EP - 67
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 1
ER -
