Inhibitory effects of methanol extracts of selected plants on the proliferation of two human melanoma cell lines

Purpose: To investigate the in vitro antiproliferative activity of methanol extracts of six plants regardless of their claimed ethnopharmacological application.Methods: Methanol extracts of different parts of Glycyrrhiza glabra L. Licorice), Matricaria chamomilla L. (Chamomile), Salvia triloba L. (Sage), Rheum palmatum L. (Rhubarb), Trigonella foenum-graecum L (Fenugreek) and Sambucus ebulus L. (Dwarf Elder)were prepared. The antiproliferative effects of the extracts weretestedon two skin cancer melanoma cell lines namely A375.S2 (low tyrosinase expression) and WM 136.1A (high tyrosinase expression) using MTT assay.The IC50 values for the active extracts were determined against the two melanoma cell lines.Results: The methanol extracts of G. glabra, M. chamomilla, S.triloba, R. palmatum inhibited the melanotic WM1361A proliferation in a dose-dependent manner revealing IC50 values of 35.2, 25.2, 20.6, 17.8, μg/ml, respectively but not A375.S2 cell line. However, the extracts of T. foenum-graecum and S. ebulus did not exhibit any significant cytotoxic activity on both melanoma cell lines.Conclusion: Methanol extracts of Licorice, Chamomile, Sage and Rhubarb have significantantiproliferative activity on WM1361A cell line; a representative human melanotic melanocyte tumor cell line. This renders these plants as potential sources of new lead compounds for the development of new drugs for melanoma cancer.Keywords: Melanoma, Plant extract, tyrosinase, Licorice, Chamomile, Sage, Rhubarb, WM1361A

Inhibitory effects of methanol extracts of selected plants on proliferation of two human melanoma cell lines

Purpose: The aim of the current study was to investigate the in vitro antiproliferative activity of methanolic extracts of six plants regardless of their claimed ethnopharmacological application.Methods: Methanol extracts of different parts of Glycyrrhizaglabra L. (Licorice), Matricaria chamomilla L. (Chamomile), Salvia triloba L. (Sage), Rheum palmatum L. (Rhubarb), Trigonella foenum-graecum L. (Fenugreek) and Sambucusebulus L. (Dwarf Elder) were prepared. The antiproliferative effects of the extracts were tested on two skin cancer melanoma cell lines namely A375.S2 (low tyrosinase expression) and WM 136.1A (high tyrosinase expression) using MTT assay. The IC50 values for the active extracts were determined against the two melanoma cell lines.Results: The methanolic extracts of G.glabra, M. chamomilla, S. triloba, R. palmatum inhibited the melanotic WM1361A proliferation in a dose-dependent manner revealing IC50 values of 35.2, 25.2, 20.6, 17.8, μg/ml, respectively but not A375.S2 cell line. However, the extracts of T. foenum-graecum and S. ebulus did not exhibit any significant cytotoxic activity on both melanoma cell lines.Conclusion: The results of these experiments show that methanol extracts of licorice, chamomile, sage and rhubarb have significant antiproliferative activity onWM1361A cell line; a representative human melanotic melanocyte tumor cell line. This renders these plants as potential sources of new lead compounds for the development of new drugs for melanoma cancer.Keywords: Melanoma, Plant extract, tyrosinase, Licorice, Chamomile, Sage, Rhubarb, WM1361

Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions

Introduction: Berberine is a natural isoquinoline alkaloid with anti-cancer properties. Nevertheless, the underlying mechanism of its action in human colorectal cancer (CRC) has not been thoroughly elucidated. We investigated the anti-cancer effect of berberine on HT-29, SW-480 and HCT-116 human CRC cell lines. Methods: Cell proliferation, migration and invasion were studied by MTT assay, wound healing, transwell chambers and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunostaining were used to evaluate the expression of aquaporins (AQPs) 1, 3 and 5 in colon cancer cell lines before and after treatment with berberine (10, 30 and 100 µM). RT-qPCR and Western blotting were used to further explore the PI3K/AKT signaling pathway and the molecular mechanisms underlying berberine-induced inhibition of cell proliferation. Results: We demonstrated that treatment of these CRC cell lines with berberine inhibited cell proliferation, migration and invasion through induction of apoptosis and necrosis. HT-29, SW-480 and HCT-116 stained positively for AQP 1, 3 and 5, and berberine treatment down-regulated the expression of all three types of AQPs. Berberine also modulated PI3K/AKT pathway activity through up-regulating PTEN and down-regulating PI3K, AKT and p-AKT expression as well as suppressing its downstream targets, mTOR and p-mTOR at the protein level. Discussion/Conclusions: These findings indicate that berberine inhibited growth, migration and invasion of these colon cancer cell lines via down-regulation of AQP 1, 3 and 5 expressions, up-regulating PTEN which inhibited the PI3K/AKT pathway at the gene and protein levels, and that AQP 1, 3 and 5 expression level can be used as prognostic biomarkers for colon cancer metastasis

Antioxidant, Antibacterial, and Cytotoxic Activities of Cedrus atlantica Organic Extracts and Essential Oil

Introduction: Cedrus atlantica is an endemic pine tree species well known for its wood oil. Its traditional medicinal usages are mainly anti-inflammatory and antibacterial. The current study aimed to explore both the essential oil of the tree\u27s cones and the organic extracts of the branches, chemically and biologically. Methods: The essential oil was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Phenolic contents of the extracts and fractions were determined following diverse methods described in the literature. The bioactivity was assessed for their antioxidant (FRAP, DPPH• and ABTS•+ radical scavenging activities), antibacterial (Broth microdilution method), and cytotoxic effects (MTT assay). Results: α-pinene (81.49%) was found to be the major constituent of the essential oil. The extracts and fractions were found to be rich in polyphenols. The antioxidant activity was better in the ethyl acetate fraction. Staphylococcus aureus appeared to be the most susceptible strain to C. atlantica\u27s extracts and oil, with a minimum inhibitory concentration and minimum bactericidal concentration values of 62.5 and 125 µg/mL for the ethyl acetate fraction, respectively, and values of 0.25 and 0.5% for the essential oil, respectively. C. atlantica\u27s essential oil exhibited a potent cytotoxic activity against MCF-7 breast cancer cell line with an IC50 value of 143.13±14.6 µg/mL. Conclusion: C. atlantica\u27s essential oil and organic extracts showed antioxidant, antibacterial, and anticancer activities. Thereby, the ethnobotanical use of C. atlantica in traditional preparations is worth investigating as the plant appears to be a potential source of interesting metabolites

Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line

Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined LDHB promoter methylation levels. An upregulation of 2.9 times of LDHB gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in LDHA gene expression levels was found. Furthermore, morphological changes in the cell shape accompanied the changes in gene expression. Bisulfate treatment followed by sequencing of the LDHB promoter was performed to track any change in methylation levels; hypomethylation of CpG areas was found, suggesting that gene expression upregulation could be due to methylation level changes. Changes in LDHA and LDHB gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML

Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS

Metabolic syndrome (MetS) is a disorder characterized by a group of factors that can increase the risk of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus (T2D). Metabolomics has provided new insight into disease diagnosis and biomarker identification. This cross-sectional investigation used an untargeted metabolomics-based technique to uncover metabolomic alterations and their relationship to pathways in normoglycemic and prediabetic MetS participants to improve disease diagnosis. Plasma samples were collected from drug-naive prediabetic MetS patients (n = 26), normoglycemic MetS patients (n = 30), and healthy (normoglycemic lean) subjects (n = 30) who met the inclusion criteria for the study. The plasma samples were analyzed using highly sensitive ultra-high-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). One-way ANOVA analysis revealed that 59 metabolites differed significantly among the three groups (p &lt; 0.05). Glutamine, 5-hydroxy-L-tryptophan, L-sorbose, and hippurate were highly associated with MetS. However, 9-methyluric acid, sphinganine, and threonic acid were highly associated with prediabetes/MetS. Metabolic pathway analysis showed that arginine biosynthesis and glutathione metabolism were associated with MetS/prediabetes, while phenylalanine, D-glutamine and D-glutamate, and lysine degradation were highly impacted in MetS. The current study sheds light on the potential diagnostic value of some metabolites in metabolic syndrome and the role of their alteration on some of the metabolic pathways. More studies are needed in larger cohorts in order to verify the implication of the above metabolites on MetS and their diagnostic value

Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives

A series of 2,3-dihydroquinazolin-4(1H)-one derivatives (3a–3m) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1H)-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5′-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k–3m. Thus, compounds 3k–3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB