TY - JOUR
T1 - Antiproliferative activity of Pt(IV)-bis(carboxylato) conjugates on malignant pleural mesothelioma cells
AU - Alessio, Manuela
AU - Zanellato, Ilaria
AU - Bonarrigo, Ilaria
AU - Gabano, Elisabetta
AU - Ravera, Mauro
AU - Osella, Domenico
N1 - Funding Information:
We thank Prof. P.-G. Betta (Mesothelioma Biobank Regional Reference Center, Alessandria National Hospital) for providing MPM and HMC cell lines. Financial support was from the Provincia di Alessandria and CRT Foundation (Turin, Italy) “Mesothelioma project” . This research was carried out within the framework of the European Union CMST COST Action CM1105 “Functional metal complexes that bind to biomolecules” and Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (CIRCMSB, Bari, Italy).
PY - 2013
Y1 - 2013
N2 - The bifunctional Pt(IV) conjugate cis,cis,trans- diamminedichloridobis(valproato)platinum(IV), based on the cisplatin square-plane with two axial valproato (2-propylpentanoate, VPA) ligands, has been re-synthesized with a modified procedure and its biological activity was compared with that of its isomer cis,cis,trans-diamminedichloridobis(n- octanoato)platinum(IV). Both complexes showed a striking cytotoxic effect (in the micro or sub-micromolar range) on various human carcinoma cell lines (namely ovarian, colon, breast and lung cancer), and, in particular, on cells derived from malignant pleural mesothelioma. This remarkable activity is due to the action of the cisplatin metabolite only, generated by the intracellular Pt(IV)→Pt(II) reduction, which concentration is greatly increased by the enhanced cellular accumulation of the original, highly lipophilic Pt(IV)-bis(carboxylato) complexes. The two axial VPA ligands are released in a too low concentration to act as histone deacetylase inhibitor (HDACI), as VPA works in the millimolar range, so that no synergism can be claimed. Moreover, n-octanoic acid is substantially deprived of any HDACI propensity.
AB - The bifunctional Pt(IV) conjugate cis,cis,trans- diamminedichloridobis(valproato)platinum(IV), based on the cisplatin square-plane with two axial valproato (2-propylpentanoate, VPA) ligands, has been re-synthesized with a modified procedure and its biological activity was compared with that of its isomer cis,cis,trans-diamminedichloridobis(n- octanoato)platinum(IV). Both complexes showed a striking cytotoxic effect (in the micro or sub-micromolar range) on various human carcinoma cell lines (namely ovarian, colon, breast and lung cancer), and, in particular, on cells derived from malignant pleural mesothelioma. This remarkable activity is due to the action of the cisplatin metabolite only, generated by the intracellular Pt(IV)→Pt(II) reduction, which concentration is greatly increased by the enhanced cellular accumulation of the original, highly lipophilic Pt(IV)-bis(carboxylato) complexes. The two axial VPA ligands are released in a too low concentration to act as histone deacetylase inhibitor (HDACI), as VPA works in the millimolar range, so that no synergism can be claimed. Moreover, n-octanoic acid is substantially deprived of any HDACI propensity.
KW - Drug delivery
KW - Histone deacetylase inhibition
KW - Platinum uptake
KW - Pt(IV) complexes
KW - Valproic acid
UR - http://www.scopus.com/inward/record.url?scp=84884605349&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2013.09.003
DO - 10.1016/j.jinorgbio.2013.09.003
M3 - Article
SN - 0162-0134
VL - 129
SP - 52
EP - 57
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -
