RESUMEN
Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2), 2,2-dimethylmalonic acid (Me2-mal, Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4) and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, were synthesized and characterized by elemental microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3 complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity of the platinum(II) complexes was investigated in human and murine cancer cell lines as well as in a normal murine cell line by MTT assay. The results show that the investigated platinum(II) complexes exhibit potent cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. The Pt3 complex shows stronger selectivity against cancer cells compared to other platinum(II) complexes tested and thus exhibits beneficial antitumor activity, mainly by inducing apoptosis and inhibiting cell proliferation and migration. The Pt3 complex also exhibits significant in vivo antitumor activity in the orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All the results indicate that these novel platinum(II) complexes have good antitumor activity on breast and colorectal cancer and have the potential to become possible candidates for cancer treatment.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Animales , Antineoplásicos/química , Línea Celular Tumoral , Complejos de Coordinación/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Malonatos/farmacología , Ratones , Platino (Metal)/química , Platino (Metal)/farmacologíaRESUMEN
The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.