Document type
Journal articles
Document subtype
Full paper
Title
[Ru(II)(eta5-C5H5)(bipy)(PPh3)]+, a promising large spectrum antitumor agent: Cytotoxic activity and interaction with human serum albumin
Participants in the publication
Ana Isabel Tomaz (Author)
Dep. Química e Bioquímica
CQE
Tamás Jakusch (Author)
Tânia S. Morais (Author)
Dep. Química e Bioquímica
Fernanda Marques (Author)
Rodrigo F.M. de Almeida (Author)
Dep. Química e Bioquímica
CQB
Filipa Mendes (Author)
Éva A. Enyedy (Author)
Isabel Santos (Author)
João Costa Pessoa (Author)
Tamás Kiss (Author)
M. Helena Garcia (Author)
Dep. Química e Bioquímica
Summary
Ruthenium complexes hold great potential as alternatives to cisplatin in cancer chemotherapy. We present results on the in vitro antitumor activity of an organometallic ‘Ru(II)Cp’ complex, [Ru(II)Cp(bipy)(PPh3)][CF3SO3], designated as TM34 (PPh3 = triphenylphosphine; bipy = 2,2′-bipyridine), against a panel of human tumor cell lines with different responses to cisplatin treatment, namely ovarian (A2780/A2780cisR, cisplatin sensitive and resistant, respectively), breast (MCF7) and prostate (PC3) adenocarcinomas. TM34 is very active against all tumorigenic cell lines, its efficacy largely surpassing that of cisplatin (CisPt). The high activity of TM34 towards CisPt resistant cell lines possibly suggests a mechanism of action distinct from that of CisPt. The effect of TM34 on the activity of the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) involved in DNA repair mechanisms and apoptotic pathways was also evaluated, and it was found to be a strong PARP-1 ruthenium inhibitor in the low micromolar range (IC50 = 1.0 ± 0.3 μM). TM34 quickly binds to human serum albumin forming a 1:1 complex with a conditional stability constant (log K′ ~ 4.0), comparable to that of the Ru(III) complex in clinical trial KP1019. This indicates that TM34 can be efficiently transported by this protein, possibly being involved in its distribution and delivery in the blood stream. Albumin binding does not affect TM34 activity, yielding an adduct that maintains cytotoxic properties (against A2780 and A2780cisR cells). Altogether, the properties herein evaluated suggest that TM34 could be an anticancer agent of highly relevant therapeutic value.
Date of Publication
2012-12
Where published
Journal of Inorganic Biochemistry
Publication Identifiers
ISSN - 0162-0134
Publisher
Elsevier BV
Number of pages
8
Starting page
261
Last page
269
Document Identifiers
DOI -
https://doi.org/10.1016/j.jinorgbio.2012.06.016
URL -
http://dx.doi.org/10.1016/j.jinorgbio.2012.06.016
Rankings
Web Of Science Q1 (2012) - 3.197 - Chemistry, Inorganic & Nuclear
SCIMAGO Q1 (2012) - 0.990 - Inorganic Chemistry
SCOPUS Q1 (2012) - 0.99 - Biochemistry
Web Of Science Q1 (2019) - 3.212 - CHEMISTRY, INORGANIC & NUCLEAR - SCIE
SCOPUS Q1 (2019) - 6 - Inorganic Chemistry
Keywords
Ruthenium(II)
Cyclopentadienyl
Anti-tumor activity
Cytotoxicity
PARP-1 inhibitor
Human serum albumin-binding