BODIPY-peptide conjugate: Synthesis, photo-physical and cell viability studies

The synthesis and biological studies of BODIPY-GPR peptide conjugate (BD-2) are reported. As compared to the parent BODIPY (BD-1), the peptide linked BD-2showed blue shifted absorption and emission with excellent Stokes shift of 201 nm. Molecular docking studies on EGFR protein kinase indicated very efficient binding affinity of BD-2 as compared to the standard drug (Erlotinib). The cell viability experiments of BD-2on normal (HEK293T) and lung cancer (A549) cell lines indicated 85–95% viability. Bioimaging studies showed that, BD-2was able to penetrate the lung cancer cell line.

EZH2 and KDM6B Expressions Are Associated with Specific Epigenetic Signatures during EMT in Non Small Cell Lung Carcinomas

The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the histone demethylase KDM6B (Lysine Demethylase 6B), which can remove the H3K27me3 mark. Nevertheless, it still remains unclear how these enzymes, with apparent opposite activities, could both promote EMT. In this study, we evaluated the function of these two enzymes using an EMT-inducible model, the lung cancer A549 cell line. ChIP-seq coupled with transcriptomic analysis showed that EZH2 and KDM6B were able to target and modulate the expression of different genes during EMT. Based on this analysis, we described INHBB, WTN5B, and ADAMTS6 as new EMT markers regulated by epigenetic modifications and directly implicated in EMT induction.

Mechanism underlying the inhibitory effect of Elaeagnus Conferta Roxb on TNF –α induced NF- kB nuclear translocation in non- small lung cancer A549 cell line using Flow cytometry

Our study examined for the inhibitory effect of ethanolic extract of Eleagnus Conferta Roxb leaves on TNF –α induced NF- kB nuclear translocation in lung cancer A549 cell line using flow cytometry. Apoptosis also studied to know about the antiproliferative and anticancer effects. However, our results revealed in apoptosis, Elaeagnus conferta Roxb leaves showed (33.54%) increased in proportion of cells. In the study of pre-treatment of A549 cells with Elaeagnus conferta Roxb leaves followed by TNF- α caused the increased proportion of cells (20.78%) at apoptosis induced cell death, which was statistically significant (p< 0.001). The untreated A549 cells had minimal NF-kB expression (0.25± 0.01%). However, the approach of A549 cells with Elaeagnus conferta Roxb had induced NF-kB production many fold (11.50± 1.05%). Therefore, we conclude our study was proved the impact of Elaeagnus conferta Roxb leaves inhibit the cellular growth of NSCLC-A549 cell line and induces apoptosis. Hence, from our findings, we proved this plant has anticancer activity, further feasibly taken for drug formulation.

Baicalein suppresses vasculogenic mimicry through inhibiting RhoA/ROCK expression in lung cancer A549 cell line

Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.

UPLC-MS/MS Phytochemical Analysis of Two Croatian Cistus Species and Their Biological Activity

Aqueous extracts of two Cistus species wild growing in Croatia—Cistus creticus (CC) and Cistus salviifolius (CS)—have been assessed with UPLC-MS/MS, showing 43 different phytochemicals, with flavonol glycosides: myricetin-3-hexoside and myricetin-rhamnoside, predominate ones in CC and myricetin-3-hexoside in CS. Antioxidant potential tested with the FRAP method showed no difference between CS and CC aqueous extracts, while higher phenolic content of CC comparing to CS, determined with a Folin–Cicolateu reagent correlated to its higher antioxidant capacity observed by the DPPH method. Both extracts were assessed for antimicrobial activity, using disc-diffusion and broth microdilution assays, targeting the opportunistic pathogens, associated with food poisoning, urinary, respiratory tract, blood stream and wound infections in humans. Antimicrobial assays revealed that fungi were in general more sensitive to both Cistus aqueous extracts, comparing to the bacteria where two extracts showed very similar activity. The most potent activity was observed against A. baumannii for both extracts. The extracts were tested on human lung cancer (A549) cell line using the MTT assay, showing very similar antiproliferative activity. After 72 h treatment with CC and CS aqueous extracts in concentration of 0.5 g/L, the viability of the cells were 37% and 50% respectively, compared to non-treated cells.

Synthesis, In Vitro Anticancer Activity and In Silico Study of some Benzylidene Hydrazide Derivatives

Some benzylidenehydrazides (3a-e) have been synthesized in three reaction steps from anthranilic acid in good yields, about 70% - 99%. The structures of the synthesized compounds were analyzed using spectroscopic methods. The compounds were evaluated its activity against human lung cancer, A549 cell line by MTT method and studied its molecular docking onto the protein tyrosine kinase (PDB ID: 1M17) by using Molegro® vs. 5.5. The data showed that N-(2-(2-(4-nitrobenzylidene)hydrazinecarbonyl)phenyl)benzamide (3d) which synthesized in 70% yield and has the highest activity on inhibiting the growth of A549 cell line with IC50 10.9μg/mL, which was linier with our in silico study. Compound 3d has the smallest RS value -94.44 kcal/mol, lower than selected Ligand, Erlotinib.