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.

Pharmacological investigation of antioxidant and anti-inflammatory activities of leaves and branches extracts from Plinia cauliflora (Jaboticaba).

ETHNOPHARMACOLOGICAL RELEVANCE: Among all native Brazilian plant species, Plinia cauliflora (DC.) Kausel (Jaboticaba), is well known for producing "superfruits", due to their high phenolic content and antioxidant property. The fruit has astringent characteristics, and it is popularly known for the treatment of diarrhea, rash, and intestinal inflammation. However, there are only a few studies on the use of leaves and branches of this species in the literature, mainly to treat oxidative stress and inflammation. AIM OF THE STUDY: The present study aimed to investigate the antioxidant and anti-inflammatory potential of leaves and branches extracts from P. cauliflora. MATERIAL AND METHODS: The phytochemical analysis of P. cauliflora extracts was performed by the total phenolic, flavonoid, and tannin dosage method. Moreover, the compounds were identified by HPLC-MS-Q-TOF. Antioxidant capacity was determined by DPPH, ß-carotene/linoleic acid system, MDA formation, and phosphomolybdenum assays. In vitro and in vivo anti-inflammatory activities of P. cauliflora were evaluated by the reduction of nitric oxide in the J774A.1 cell line and inhibition of ear edema in mice, respectively. RESULTS: The ethanolic extract of the leaves exhibited greater flavonoid content whereas the ethanolic extract of the branches showed higher tannins content. Twenty-two and seventeen compounds were identified by HPLC-MS-Q-TOF in the leaves and branches, respectively, being tellimagrandin I, castalagin, and valoneic acid dilactone reported for the first time in P. cauliflora. The antioxidant potential of extracts was confirmed through different oxidation pathways from oxidizing radicals, which might be related to the presence of phenolic compounds. For the anti-inflammatory assay, the leaves and branches extracts showed promising results, with a reduction of nitric oxide ear edema inhibition around 95% and 80%, respectively. CONCLUSIONS: Herein, the great biological potential of leaves and branches extracts from P. cauliflora was highlighted. These parts of the plant are underused and poorly reported in the literature, especially for the antioxidant and anti-inflammatory activities.

Contributions of cytogenetics to cancer research / Contribuições da citogenética em pesquisas sobre o câncer

The two conflicting visions of tumorigenesis that are widely discussed are the gene-mutation hypothesis and the aneuploidy hypothesis. In this review we will summarize the contributions of cytogenetics in the study of cancer cells and propose a hypothetical model to explain the influence of cytogenetic events in carcinogenesis, emphasizing the role of aneuploidy. The gene mutation hypothesis states that gene-specific mutations occur and that they maintain the altered phenotype of the tumor cells, and the aneuploidy hypothesis states that aneuploidy is necessary and sufficient for the initiation and progression of malignant transformation. Aneuploidy is a hallmark of cancer and plays an important role in tumorigenesis and tumor progression. Aneuploid cells might be derived from polyploid cells, which can arise spontaneously or are induced by environmental agents or chemical compounds, and the genetic instability observed in polyploid cells leads to chromosomal losses or rearrangements, resulting in variable aberrant karyotypes. Because of the large amount of evidence indicating that the correct chromosomal balance is crucial to cancer development, cytogenetic techniques are important tools for both basic research, such as elucidating carcinogenesis, and applied research, such as diagnosis, prognosis and selection of treatment. The combination of classic cytogenetics, molecular cytogenetics and molecular genetics is essential and can generate a vast amount of data, enhancing our knowledge of cancer biology and improving treatment of this disease.

As duas visões conflitantes da tumorigênese que são amplamente discutidas são a hipótese da mutação gênica e a hipótese da aneuploidia. Nesta revisão vamos resumir as contribuições da citogenética no estudo das células tumorais e propor um modelo hipotético para explicar a influência dos eventos citogenéticos na carcinogênese, enfatizando o papel da aneuploidia. A teoria da mutação gênica estabelece que mutações específicas ocorrem e mantêm o fenótipo alterado das células de um tumor, enquanto a hipótese da aneuploidia estabelece que a aneuploidia é necessária e suficiente para a iniciação e progressão da transformação maligna. A aneuploidia é considerada um marcador do câncer e esta desempenha um importante papel tanto na tumorigênese, quanto na progressão tumoral. Células aneuplóides podem ser derivadas de células poliplóides, que surgem espontaneamente ou são induzidas por agentes ambientais ou compostos químicos. A instabilidade genética observada em células poliplóides leva a perdas ou rearranjos cromossômicos, resultando em cariótipos variavelmente aberrantes. Devido à grande quantidade de evidências indicando que um balanço cromossômico correto é crucial para o desenvolvimento do câncer, as técnicas citogenéticas são ferramentas importantes tanto para a pesquisa básica, tais como pesquisas para elucidar a carcinogênese, quanto pesquisas aplicadas, como no diagnóstico, prognóstico e escolha do tratamento. A combinação da citogenética clássica, citogenética molecular e genética molecular é essencial e pode gerar uma grande quantidade de dados, aumentando o nosso conhecimento da biologia do câncer, melhorando assim o tratamento desta doença.