Copper(II) Complex Containing 4-Fluorophenoxyacetic Acid Hydrazide and 1,10-Phenanthroline: A Prostate Cancer Cell-Selective and Low-Toxic Copper(II) Compound.

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

In vitro cytotoxic and genotoxic analysis of Garcinia humilis crude extract

Garcinia humilis, known commonly as achachairú or bacupari, has great medicinal value. Their fruits have pharmacological, antibacterial, antioxidant, and anticancer properties. Therefore, the objective of the present study was to evaluate the cytotoxicity and genotoxicity of G. humilis crude extract in breast tumor cells. Cytotoxicity was determined using the Resazurin reduction assay and genotoxicity by the single cell gel electrophoresis assay (Comet assay) on human MCF-7 cells. Crude extract of G. humilis was cytotoxic only when used at high concentrations (IC50 = 5.084 mg mL-1). The Comet assay showed that the crude extract did not induce genotoxicity at 1 and 5 mg mL-1 but did show signs of DNA fragmentation and DNA fragmentation at 10 mg mL-1. The cytotoxic activity against breast adenocarcinoma cells at high concentrations suggests that this medicinal plant could be used with caution and must be further studied to understand better its therapeutic and toxicological potential in the human body.

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells.

The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.

Using native and invasive livebearing fishes (Poeciliidae, Teleostei) for the integrated biological assessment of pollution in urban streams.

Invasive species are increasingly replacing native species, especially in anthropogenically transformed or polluted habitats. This opens the possibility to use invasive species as indicator taxa for the biological assessment of pollution. Integrated biological assessment, however, additionally relies on the application of multiple approaches to quantify physiological or cytogenetic responses to pollution within the same focal species. This is challenging when species are restricted to either polluted or unpolluted sites. Here, we make use of a small group of neotropical livebearing fishes (family Poeciliidae) for the integrated biological assessment of water quality. Comparing urban and suburban stream sections that receive varying degrees of pollution from industrial and domestic waste waters in and around the Brazilian city of Uberlândia, we demonstrate that two members of this family may indeed serve as indicators of water pollution levels. The native species Phalloceros caudimaculatus appears to be replaced by invasive guppies (Poecilia reticulata) at heavily polluted sites. Nevertheless, we demonstrate that both species could be used for the assessment of bioaccumulation of heavy metals (Pb, Cu, and Cr). Ambient (sediment) concentrations predicted concentrations in somatic tissue across species (R2-values between 0.74 and 0.96). Moreover, we used cytogenetic methods to provide an estimate of genotoxic effects of water pollution and found pollution levels (multiple variables, condensed into principal components) to predict the occurrence of nuclear abnormalities (e.g., frequencies of micro-nucleated cells) across species (R2 between 0.69 and 0.83). The occurrence of poeciliid fishes in urban and polluted environments renders this family a prime group of focal organisms for biological water quality monitoring and assessment. Both species could be used interchangeably to assess genotoxic effects of water pollution, which may facilitate future comparative analyses over extensive geographic scales, as members of the family Poeciliidae have become invasive in tropical and subtropical regions worldwide.