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)(PPh(3))][CF(3)SO(3)], designated as TM34 (PPh(3) =
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 (IC(50)=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 if the complex is introduced 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.