Induction of Apoptosis and Cell Cycle Blockade by Helichrysetin in A549 Human Lung Adenocarcinoma Cells

Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent

Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer

The role of chalcones: helichrysetin, xanthohumol, and flavokawin-C in promoting neurite outgrowth in PC12 Adh cells

<p>Chalcones are a group of compounds widely distributed in plant kingdom. The aim of this study was to assess the neurite outgrowth stimulatory activity of selected chalcones, namely helichrysetin, xanthohumol and flavokawin-C. Using adherent rat pheochromocytoma (PC12 Adh) cells, the chalcones were subjected to neurite outgrowth assay and the extracellular nerve growth factor (NGF) levels were determined. Xanthohumol (10 μg/mL) displayed the highest (<i>p</i> < 0.05) percentage of neurite-bearing PC12 Adh cells and the highest (<i>p</i> < 0.05) NGF level in the culture medium of xanthohumol-treated cells. While, helichrysetin induced a moderately high numbers of neurite-bearing cells, flavokawin-C did not stimulate neurite outgrowth. This work supports the potential use of xanthohumol as a potential neuroactive compound to stimulate neurite outgrowth.</p

Interactive effects of temperature and copper toxicity on photosynthetic efficiency and metabolic plasticity in Scenedesmus quadricauda (Chlorophyceae)

Warming and copper (Cu) toxicity are two key abiotic stressors that strongly affect cell growth, photosynthetic rate, and metabolism in microalgae. In this study, a freshwater chlorophyte, Scenedesmus quadricauda, was exposed to various concentrations of copper sulfate (300, 600, and 1000 μM nominal concentrations of CuSO4·5H2O) at 25 and 35 °C. The changes in cell density, photosynthetic parameters, in vivo absorption spectra, reactive oxygen species (ROS) levels, and metabolic profile were analyzed. The effects of copper toxicity on the physiology and biochemistry of microalgae were highly dependent on water temperature. The interactive effects of both stressors induced significant impact on the photosynthetic parameters such as maximum quantum yield (Fv/Fm), saturation irradiance (Ek), and non-photochemical quenching (NPQ). Temperature induced significant impact on cell density, Ek and NPQ, while the Cu toxicity significantly affected the Fv/Fm and NPQ. Changes in the in vivo absorption spectra and high levels of reactive oxygen species (ROS) were observed across different treatments. Overall, S. quadricauda adapted to the two abiotic stresses via NPQ and metabolic restructuring. Key metabolites including glycine, proline, hexadecanoic acid, propanoic acid, octadecanoic acid, galactose, lactose, and sucrose were involved in the microalgal response. The synergistic effects of temperature and Cu stresses on microalgae might affect community tolerance and species distribution in the long run

Physiological and metabolic responses of Scenedesmus quadricauda (Chlorophyceae) to nickel toxicity and warming

An ecologically important tropical freshwater microalga, Scenedesmus quadricauda, was exposed to Ni toxicity under two temperature regimes, 25 and 35 °C to investigate the interactive effects of warming and different Ni concentrations (0.1, 1.0 and 10.0 ppm). The stress responses were assessed from the growth, photosynthesis, reactive oxygen species (ROS) generation and metabolomics aspects to understand the effects at both the physiological and biochemical levels. The results showed that the cell densities of the cultures were higher at 35 °C compared to 25 °C, but decreased with increasing Ni concentrations at 35 °C. In terms of photosynthetic efficiency, the maximum quantum yield of photosystem II (Fv/Fm) of S. quadricauda remained consistent across different conditions. Nickel concentration at 10.0 ppm affected the maximum rate of relative electron transport (rETRm) and saturation irradiance for electron transport (Ek) in photosynthesis. At 25 °C, the increase of non-photochemical quenching (NPQ) values in cells exposed to 10.0 ppm Ni might indicate the onset of thermal dissipation process as a self-protection mechanism against Ni toxicity. The combination of warming and Ni toxicity induced a strong oxidative stress response in the cells. The ROS level increased significantly by 40% after exposure to 10.0 ppm of Ni at 35 °C. The amount of Ni accumulated in the biomass was higher at 25 °C compared to 35 °C. Based on the metabolic profile, temperature contributed the most significant differentiation among the samples compared to Ni treatment and the interaction between the two factors. Amino acids, sugars and organic acids were significantly regulated by the combined factors to restore homeostasis. The most affected pathways include sulphur, amino acids, and nitrogen metabolisms. Overall, the results suggest that the inhibitory effect of Ni was lower at 35 °C compared to 25 °C probably due to lower metal uptake and primary metabolism restructuring. The ability of S. quadricauda to accumulate substantial amount of Ni and thrive at 35 °C suggests the potential use of this strain for phycoremediation and outdoor wastewater treatment

3D printed bio-models for medical applications

Purpose - The design process of a bio-model involves multiple factors including data acquisition technique, material requirement, resolution of the printing technique,cost effectiveness of the printing process and end use requirements.This paper aims to compare and highlight the effects of these design factors on the printing outcome of bio-models. Design/methodology/approach - Different data sources including engineering drawing, computed tomography (CT), and optical coherence tomography (OCT) were converted to a printable data format. Three different bio-models, namely, an ophthalmic model, a retina model and a distal tibia model, were printed using two different techniques, namely, PolyJet and fused deposition modelling. The process flow and 3D printed models were analysed. Findings - The data acquisition and 3D printing process affect the overall printing resolution. The design process flows using different data sources were established and the bio-models were printed successfully. Research limitations/implications - Data acquisition techniques contained inherent noise data and resulted in inaccuracies during data conversion. Originality/value - This work showed that the data acquisition and conversion technique had a significant effect on the quality of the bio-model blueprint and subsequently the printing outcome. In addition, important design factors of bio-models were highlighted such as material requirement and the cost-effectiveness of the printing technique. This paper provides a systematic discussion for future development of an engineering design process in three-dimensional (3D) printed bio-models.Accepted versio

Pentacyclic and hexacyclic cucurbitacins from Elaeocarpus petiolatus

Four undescribed cucurbitacins, designated as petiolaticins A–D, and four known cucurbitacins were isolated from the bark and leaves of Elaeocarpus petiolatus (Jack) Wall. Their chemical structures were elucidated based on detailed analyses of the NMR and MS data. The absolute configuration of petiolaticin A was also determined by X-ray diffraction analysis. Petiolaticin A represents a cucurbitacin derivative incorporating a 3,4-epoxyfuranyl-bearing side chain, while petiolaticin B possesses a furopyranyl unit fused to the tetracyclic cucurbitane core structure. Petiolaticins A, B, and D were evaluated in vitro against a panel of human breast, pancreatic, and colorectal cancer cell lines. Petiolaticin A exhibited the greatest cytotoxicity against the MDA-MB-468, MDA-MB-231, MCF-7, and SW48 cell lines (IC50 7.4, 9.2, 9.3, and 4.6 μM, respectively). Additionally, petiolaticin D, 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one, and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside were tested for their ability to inhibit cell entry of a pseudotyped virus bearing the hemagglutinin envelope protein of a highly pathogenic avian influenza virus. Petiolaticin D showed the highest inhibition (44.3%), followed by 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (21.0%), and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside showed limited inhibition (9.0%). These preliminary biological assays have demonstrated that petiolaticins A and D possess anticancer and antiviral properties, respectively, which warrant for further investigations

3D printed bio-models for medical applications

Purpose - The design process of a bio-model involves multiple factors including data acquisition technique, material requirement, resolution of the printing technique,cost effectiveness of the printing process and end use requirements.This paper aims to compare and highlight the effects of these design factors on the printing outcome of bio-models. Design/methodology/approach - Different data sources including engineering drawing, computed tomography (CT), and optical coherence tomography (OCT) were converted to a printable data format. Three different bio-models, namely, an ophthalmic model, a retina model and a distal tibia model, were printed using two different techniques, namely, PolyJet and fused deposition modelling. The process flow and 3D printed models were analysed. Findings - The data acquisition and 3D printing process affect the overall printing resolution. The design process flows using different data sources were established and the bio-models were printed successfully. Research limitations/implications - Data acquisition techniques contained inherent noise data and resulted in inaccuracies during data conversion. Originality/value - This work showed that the data acquisition and conversion technique had a significant effect on the quality of the bio-model blueprint and subsequently the printing outcome. In addition, important design factors of bio-models were highlighted such as material requirement and the cost-effectiveness of the printing technique. This paper provides a systematic discussion for future development of an engineering design process in three-dimensional (3D) printed bio-models.Accepted versio

Metabolic and physiological regulation of Chlorella sp. (Trebouxiophyceae, Chlorophyta) under nitrogen deprivation

A freshwater green microalgae Chlorella sp., UMACC344 was shown to produce high lipid content and has the potential to be used as feedstock for biofuel production. In this study, photosynthetic efficiency, biochemical profiles and non-targeted metabolic profiling were studied to compare between the nitrogen-replete and deplete conditions. Slowed growth, change in photosynthetic pigments and lowered photosynthetic efficiency were observed in response to nitrogen deprivation. Biochemical profiles of the cultures showed an increased level of carbohydrate, lipids and total fatty acids, while the total soluble protein content was lowered. A trend of fatty acid saturation was observed in the nitrogen-deplete culture with an increase in the level of saturated fatty acids especially C16:0 and C18:0, accompanied by a decrease in proportions of monounsaturated and polyunsaturated fatty acids. Fifty-nine metabolites, including amino acids, lipids, phytochemical compounds, vitamins and cofactors were significantly dysregulated and annotated in this study. Pathway mapping analysis revealed a rewiring of metabolic pathways in the cells, particularly purine, carotenoid, nicotinate and nicotinamide, and amino acid metabolisms. Within the treatment period of nitrogen deprivation, the key processes involved were reshuffling of nitrogen from proteins and photosynthetic machinery, together with carbon repartitioning in carbohydrates and lipids