Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines.

Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.

Organotin(IV)-loaded mesoporous silica as a biocompatible strategy in cancer treatment.

The strong therapeutic potential of an organotin(IV) compound loaded in nanostructured silica (SBA-15pSn) is demonstrated: B16 melanoma tumor growth in syngeneic C57BL/6 mice is almost completely abolished. In contrast to apoptosis as the basic mechanism of the anticancer action of numerous chemotherapeutics, the important advantage of this SBA-15pSn mesoporous material is the induction of cell differentiation, an effect unknown for metal-based drugs and nanomaterials alone. This non-aggressive mode of drug action is highly efficient against cancer cells but is in the concentration range used nontoxic for normal tissue. JNK (Jun-amino-terminal kinase)-independent apoptosis accompanied by the development of the melanocyte-like nonproliferative phenotype of survived cells indicates the extraordinary potential of SBA-15pSn to suppress tumor growth without undesirable compensatory proliferation of malignant cells in response to neighboring cell death.

Anticancer potential of (pentamethylcyclopentadienyl)chloridoiridium(III) complexes bearing κP and κP,κS-coordinated Ph2 PCH2 CH2 CH2 S(O)x Ph (x=0-2) ligands.

Iridium(III) complexes of the type [Ir(η(5) -C5 Me5 )Cl2 {Ph2 PCH2 CH2 CH2 S(O)x Ph-κP}] (x=0-2; 1-3) and [Ir(η(5) -C5 Me5 )Cl{Ph2 PCH2 CH2 CH2 S(O)x Ph-κP,κS}][PF6 ] (x=0-1; 4 and 5) with 3-(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2 PCH2 CH2 CH2 S(O)x Ph were designed, synthesized, and characterized fully, including X-ray diffraction analyses for complexes 3 and 4. In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF-7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC50 values up to about 0.1 µM, representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal-based anticancer agents.

Platinum(II/IV) complexes containing ethylenediamine-N,N'-di-2/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells.

Several new R(2)eddp (R = i-Pr, i-Bu; eddp = ethylenediamine-N,N'-di-3-propionate) esters and corresponding platinum(ii) and platinum(iv) complexes of the general formula [PtCl(n)(R(2)edda-type)] (n = 2, 4) were synthesized and characterized by spectroscopic methods (IR, (1)H and (13)C NMR) and elemental analysis. The crystal structure of platinum(iv) complex [PtCl(4){(c-Pe)(2)eddip}] (3a) was resolved and is given herein. Ligand precursors, platinum(ii), and platinum(iv) complexes were tested against eight tumor cell lines (CT26CL25, HTC116, SW620, PC3, LNCaP, U251, A375, and B16). Selectivity in the action of those compounds between tumor and two normal primary cells (fibroblasts and keratinocytes) are discussed. A structure-activity relationship of these compounds is discussed. Furthermore, cell cycle distribution, induction of necrosis, apoptosis, autophagy, anoikis, caspase activation, ROS, and RNS are presented on the cisplatin-resistant colon carcinoma HCT116 cell line.