Abstract
Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.
Highlights
Resistance and toxicity of currently available chemotherapeutic agents remain major problems in cancer therapy
We found that the Cu(II) complex could inhibit tumor growth at doses which was not associated with toxicity
The Nasopharyngeal cancer (NPC) cell lines, HK1 and C666-1-green fluorescent protein (GFP)-Luc2 were maintained in an exponential growth phase in RPMI-1640 medium (Gibco, Life Technologies, Carlsbad, CA, USA) supplemented with 10% heat-inactivated fetal calf serum (FCS; Gibco), 100 U/ml penicillin (Gibco), 100 μg/ml streptomycin (Gibco), 0.25 μg/ml fungizone (Gibco) and 1X glutamax (Gibco) at 37 ̊C in a 5% CO2 humidified atmosphere
Summary
Resistance and toxicity of currently available chemotherapeutic agents remain major problems in cancer therapy. New anticancer drugs with greater effectiveness but reduced toxic side effects would be most useful. Fewer platinum compounds are entering clinical trials and this has been attributed to their inherent resistance, systemic toxicity and severe side effects and due to a shift in the design and development of anticancer metallodrugs [1,2,3,4,5]. Via the function of the metal and ligand moieties [6].
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