Melatonin and its derivative disrupt cancer stem-like phenotypes of lung cancer cells via AKT downregulation.

Cancer stem cells (CSCs), a small subpopulation of tumour cells, have properties of self-renewal and multipotency, which drive cancer progression and resistance to current treatments. Compounds potentially targeting CSCs have been recently developed. This study shows how melatonin, an endogenous hormone synthesised by the pineal gland, and its derivative suppress CSC-like phenotypes of human non-small cell lung cancer (NSCLC) cell lines, H460, H23, and A549. The effects of MLT and its derivative, acetyl melatonin (ACT), on CSC-like phenotypes were investigated using assays for anchorage-independent growth, three-dimensional spheroid formation, scratch wound healing ability, and CSC marker and upstream protein signalling expression. Enriched CSC spheroids were used to confirm the effect of both compounds on lung cancer cells. MLT and ACT inhibited CSC-like behaviours by suppression of colony and spheroid formation in NSCLC cell lines. Their effects on spheroid formation were confirmed in CSC-enriched H460 cells. CSC markers, CD133 and ALDH1A1, were depleted by both compounds. The behaviour and factors associated to epithelial-mesenchymal transition, as indicated by cell migration and the protein vimentin, were also decreased by MLT and ACT. Mechanistically, MLT and ACT decreased the expression of stemness proteins Oct-4, Nanog, and ß-catenin by reducing active AKT (phosphorylated AKT). Suppression of the AKT pathway was not mediated through melatonin receptors. This study demonstrates a novel role, and its underlying mechanism, for MLT and its derivative ACT in suppression of CSC-like phenotypes in NSCLC cells, indicating that they are potential candidates for lung cancer treatment.

Oviposition Deterrent Efficacy and Characteristics of a Botanical Natural Product, Ocimum gratissimum (L.) Oil-Alginate Beads, against Aedes aegypti (L.).

This study was aimed at investigating the oviposition deterrent activity of Ocimum gratissimum (L.) essential oil (O. gratissimum oil) and its product, Ocimum gratissimum (L.)- alginate beads (beads), against Aedes aegypti (Ae. aegypti) mosquitoes. Chemical analysis of O. gratissimum oil obtained by hydrodistillation, using gas chromatography-mass spectroscopy techniques, presented eugenol (67.38%) and Z-ß-ocimene (14.95 %) as major constituents. Good characteristics of beads were obtained by the orifice-ionic gelation method with calcium chloride as hardening agent and Tween®20 as emulsifier. The beads exhibited a good spherical shape and good hardness and flexibility with an average size of 1.49 ± 1.36 mm. The oil content, the yield percentage, and the entrapping efficiency were also examined. The beads (formulation code, F2) could prolong the essential oil release until the 10th d. This beads provided a remarkably longer oviposition deterrence activity against gravid Ae. aegypti with high percentage for 27 d, whereas free O. gratissimum oil showed a short period of time (8 d) in this activity. The stability study showed the stability of oil content and its compositions in storage condition. These results are very affordable approaches to control the dengue fever.

Grammatophyllum speciosum Ethanolic Extract Promotes Wound Healing in Human Primary Fibroblast Cells.

Grammatophyllum speciosum is a plant in Orchidaceae family which contains a variety of phytochemical compounds that might be beneficial for medicinal use. This study aimed to evaluate the activity of pseudobulb of G. speciosum extract (GSE) in wound healing processes in human primary fibroblast cells along with in vitro antioxidant activity and total phenolic content of GSE. Scratch wound healing assay indicated that GSE was capable of increasing migration rate after 6 and 9 hours of treatment. Besides, the extract was able to scavenge DPPH, ABTS, and superoxide anion radicals indicating the antioxidative property of GSE. This study suggested a novel role of the of pseudobulb extract of G. speciosum as a wound healing enhancer. The results from this study might be beneficial for the development of further novel active compounds for skin wound healing.

Spray-dried mucoadhesive microspheres: preparation and transport through nasal cell monolayer.

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceeding 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 mum were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS > CP:H > CP > H, while the rank order of swelling was CP > CS > H. Increasing the amount of CP in CP:H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP:H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP:H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging.

Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer.

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceedings 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 µm were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS>CP: H>CP>H, while the rank order of swelling was CP>CS>H. Increasing the amount of CP in CP∶H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP∶H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP∶H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging.