Antiproliferative Effects of Methanolic Root Extracts of Eichhornia crassipes Against a Skin Melanoma Cell Line: An In Vitro Study.

Background Melanoma is the most aggressive form of skin cancer, accounting for 3% of all malignant cancers. Phytochemicals and their related compounds are found in various parts of the plant Eichhornia crassipes and have a variety of pharmacological actions. The current research was intended to compare and evaluate the anti-proliferative action of methanolic extracts of E. crassipes roots and petioles against the Sloan Kettering Melanoma (SK-Mel-5) cell line. Materials and methods The waters around Ezhikkara, Ernakulum, Kerala, were discovered to contain E. crassipes. We used a Soxhlet extractor to get this concentrated liquid. For this test, we employed a methanolic extract of roots and petioles to determine the extent to which different concentrations of the extract inhibited cell proliferation. Data on absorbance were reported as a mean standard deviation. Using Probit analysis, the IC50 was calculated by evaluating the gradient of the regression line to get a value. Results Concentrations of methanolic root and petiole extracts of 12.5 µg/ml, 25 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml were analyzed. The methanol petiole extract reduced the viability of SK-Mel-5 cells more than the root extract, with IC50 values of 323.59 µg/ml and 174.70 µg/ml of the test sample concentration, respectively. The regression equation for the root extract was y = -0.1264x + 90.902 and R2 = 0.845, and for the petiole extract, it was y = -0.2187x + 88.206 and R2 = 0.917. Conclusion The current study found that increasing the concentration of methanolic extracts of roots and petioles of E. crassipes exhibited an increased cell growth inhibition rate. However, methanolic petiole extracts were more cytotoxic than the roots. Thus, the current study demonstrated the therapeutic use of E. crassipes as an anticancer agent, thereby providing a valuable alternative for enabling the early management of melanoma.

Integrin αvß3-Akt signalling plays a role in radioresistance of melanoma.

Melanoma is a deadly type of skin cancer that is particularly difficult to treat owing to its resistance to radiation therapy. Here, we attempted to determine the key proteins responsible for melanoma radioresistance, with the aim of improving disease response to radiation therapy. Two melanoma cell lines, SK-Mel5 and SK-Mel28, with different radiosensitivities were analysed via RNA-Seq (Quant-Seq) and target proteins with higher abundance in the more radioresistant cell line, SK-Mel28, identified. Among these proteins, integrin αvß3, a well-known molecule in cell adhesion, was selected for analysis. Treatment of SK-Mel28 cells with cilengitide, an integrin αvß3 inhibitor, as well as γ-irradiation resulted in more significant cell death than γ-irradiation alone. In addition, Akt, a downstream signal transducer of integrin αvß3, showed high basic activation in SK-Mel28 and was significantly decreased upon co-treatment with cilengitide and γ-irradiation. MK-2206, an Akt inhibitor, exerted similar effects on the SK-Mel28 cell line following γ-irradiation. Our results collectively demonstrate that the integrin αvß3-Akt signalling pathway contributes to radioresistance in SK-Mel28 cells, which may be manipulated to improve therapeutic options for melanoma.

Antimelanogenesis Effects of Fungal Exopolysaccharides Prepared from Submerged Culture of Fomitopsis castanea Mycelia.

Fungal exopolysaccharides are important natural products having diverse biological functions. In this study, exopolysaccharides from Fomitopsis castanea mycelia (FEPS) were prepared, and the highest mushroom tyrosinase inhibitory activity was found. FEPS were prepared from cultivation broth by ethanol precipitation method. The extraction yield and protein concentration of FEPS were 213.1 mg/l and 0.03%, respectively. FEPS inhibited mushroom tyrosinase with the half maximal inhibitory concentration (IC50) of 16.5 mg/ml and dose-dependently inhibited cellular tyrosinase activity (63.9% at 50 µg/ml, and 83.3% at 100 µg/ml) in the cell-free extract of SK-MEL-5 human melanoma cell and α-melanocytestimulating hormone (α-MSH)-stimulated melanin formation in intact SK-MEL-5 human melanoma cell. The IC50 of FEPS against NO production from RAW264.7 macrophage cells was 42.8 ± 0.64 µg/ml. By in vivo study using a zebrafish model, exposure of FEPS at 400 µg/ml to dechorionated zebrafish embryos for 18 h decreased the pigment density, compared to that without FEPS-treated control.

Development of QSAR machine learning-based models to forecast the effect of substances on malignant melanoma cells.

SK-MEL-5 is a human melanoma cell line that has been used in various studies to explore new therapies against melanoma in different in vitro experiments. Based on this study we report on the development of quantitative structure-activity relationship (QSAR) models able to predict the cytotoxic effect of diverse chemical compounds on this cancer cell line. The dataset of cytotoxic and inactive compounds were downloaded from the PubChem database. It contains the data for all chemical compounds for which cytotoxicity results expressed by GI50 was recorded. In total 13 blocks of molecular descriptors were computed and used, after appropriate pre-processing in building QSAR models with four machine learning classifiers: Random forest (RF), gradient boosting, support vector machine and random k-nearest neighbors. Among the 186 models reported none had a positive predictive value (PPV) higher than 0.90 in both nested cross-validation and on an external dataset testing, but 7 models had a PPV higher than 0.85 in both evaluations, all seven using the RFs algorithm as a classifier, and topological descriptors, information indices, 2D-autocorrelation descriptors, P-VSA-like descriptors, and edge-adjacency descriptors as sets of features used for classification. The y-scrambling test was associated with considerably worse performance (confirming the non-random character of the models) and the applicability domain was assessed through three different methods.