Behaviour of four different B16 murine melanoma cell sublines: C57BL/6J skin.

Transplantable murine melanomas are well-established models for the study of experimental cancer therapies. The aim of this study was to explore the behaviour of four different B16 murine melanoma cell sublines after inoculation into C57BL/6J mice; and, more specifically to analyse skin changes, with respect to two specific parameters: clinical (tumour volume, melanin amount, erythema) and histological (H & E, S100, VEGF expression). Both non-invasive and invasive analysis showed that B164A5 is the most aggressive melanoma cell line for C57BL/6J's skin, followed by B16F10 and then by diminished aggressive growth pattern by the B16GMCSF and B16FLT3 cell lines.

Evaluation of phenolic profile, antioxidant and anticancer potential of two main representants of Zingiberaceae family against B164A5 murine melanoma cells.

BACKGROUND: Curcuma longa Linnaeus and Zingiber officinale Roscoe are two main representatives of Zingiberaceae family studied for a wide range of therapeutic properties, including: antioxidant, anti-inflammatory, anti-angiogenic, antibacterial, analgesic, immunomodulatory, proapoptotic, anti-human immunodeficiency virus properties and anticancer effects. This study was aimed to analyse the ethanolic extracts of Curcuma rhizome (Curcuma longa Linnaeus) and Zingiber rhizome (Zingiber officinale Roscoe) in terms of polyphenols, antioxidant activity and anti-melanoma potential employing the B164A5 murine melanoma cell line. RESULTS: In order to evaluate the total content of polyphenols we used Folin-Ciocâlteu method. The antioxidant activity of the two ethanolic extracts was determined by DPPH assay, and for the control of antiproliferative effect it was used MTT proliferation assay, DAPI staining and Annexin-FITC-7AAD double staining test. Results showed increased polyphenols amount and antioxidant activity for Curcuma rhizome ethanolic extract. Moreover, 100 µg/ml of ethanolic plant extract from both vegetal products presented in a different manner an antiproliferative, respectively a proapoptotic effect on the selected cell line. CONCLUSIONS: The study concludes that Curcuma rhizome may be a promising natural source for active compounds against malignant melanoma.

Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells.

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl2 and CuSO4 aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.

Pharmaceutical Mixtures: Still A Concern for Human and Environmental Health.

In the present work, recent data on the sources, occurrence and fate of human-use pharmaceutical active compounds (PhACs) in the aquatic environment have been reviewed. Since PhACs and their metabolites are usually present as mixtures in the environment at very low concentrations, a particular emphasis was placed onto the PhACs mixtures, as well as on their short-term and long-term effects against human and environmental health. Moreover, a general overview of the main conventional as well as of the latest trends in wastewaters decontaminant technologies was outlined. Advantages and disadvantages of current processes were also pointed out. It appears that numerous gaps still exist in the current knowledge related to this field of interest, and further studies should be conducted at the global level in order to ensure a more efficient monitorisation of the presence of PhACs and their metabolites into the aquatic environment and to develop new mitigation measures.

Short-term effects of very low dose cadmium feeding on copper, manganese and iron homeostasis: A gastropod perspective.

The available information on the interplay between low-dose cadmium intake and copper, manganese, and iron homeostasis in invertebrates is limited. We have currently studied the accumulation of these trace metals in the hepatopancreas of adult snails, Cantareus aspersus, following 14 and 28 days of exposure to low doses of dietary cadmium, up to 1 mg/kg dw (dry weight). The cadmium dose, but not the duration of exposure, had a significant effect on hepatopancreas copper deposition, the values being significantly elevated compared to controls. A significant peak in manganese levels at 14 days was found in snails administered the lowest cadmium dose. These increases occurred even in the absence of cadmium increase in the hepatopancreas. Our data suggest that low dose cadmium feeding can produce a transient disturbance in hepatopancreas copper and manganese homeostasis. Such responses may serve as early biomarkers of physiological changes occurring during the initial stages of cadmium intoxication.

Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity.

Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability.

Design, Synthesis and Biological Activity Evaluation of S-Substituted 1H-5-Mercapto-1,2,4-Triazole Derivatives as Antiproliferative Agents in Colorectal Cancer.

Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.

The Cytotoxic Effects of Betulin-Conjugated Gold Nanoparticles as Stable Formulations in Normal and Melanoma Cells.

Gold nanoparticles are currently investigated as theranostics tools in cancer therapy due to their proper biocompatibility and increased efficacy related to the ease to customize the surface properties and to conjugate other molecules. Betulin, [lup-20(29)-ene-3ß, 28-diol], is a pentacyclic triterpene that has raised scientific interest due to its antiproliferative effect on several cancer types. Herein we described the synthesis of surface modified betulin-conjugated gold nanoparticles using a slightly modified Turkevich method. Transmission electron microscopy (TEM) imaging, dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of obtained gold nanoparticles. Cytotoxic activity and apoptosis assessment were carried out using the MTT and Annexin V/PI apoptosis assays. The in vitro results showed that betulin coated gold nanoparticles presented a dose-dependent cytotoxic effect and induced apoptosis in all tested cell lines.

Evaluation of phenolic profile, antioxidant and anticancer potential of two main representants of Zingiberaceae family against B164A5 murine melanoma cells

BACKGROUND: Curcuma longa Linnaeus and Zingiber officinale Roscoe are two main representatives ofZingiberaceae family studied for a wide range of therapeutic properties, including: antioxidant, anti-inflammatory, anti-angiogenic, antibacterial, analgesic, immunomodulatory, proapoptotic, anti-human immunodeficiency virus properties and anticancer effects. This study was aimed to analyse the ethanolic extracts of Curcuma rhizome (Curcuma longa Linnaeus) and Zingiber rhizome (Zingiber officinale Roscoe) in terms of polyphenols, antioxidant activity and anti-melanoma potential employing the B164A5 murine melanoma cell line. RESULTS: In order to evaluate the total content of polyphenols we used Folin-Ciocâlteu method. The antioxidant activity of the two ethanolic extracts was determined by DPPH assay, and for the control of antiproliferative effect it was used MTT proliferation assay, DAPI staining and Annexin-FITC-7AAD double staining test. Results showed increased polyphenols amount and antioxidant activity forCurcuma rhizome ethanolic extract. Moreover, 100 μg/ml of ethanolic plant extract from both vegetal products presented in a different manner an antiproliferative, respectively a proapoptotic effect on the selected cell line. CONCLUSIONS: The study concludes that Curcuma rhizome may be a promising natural source for active compounds against malignant melanoma.