BackgroundNon-small cell lung cancer (NSCLC) patients with L858R or exon 19 deletion mutations in epidermal growth factor receptor (EGFR) have good responses to the tyrosine kinase inhibitor (TKI), gefitinib. However, patients with wild-type EGFR and acquired mutation in EGFR T790M are resistant to gefitinib treatment. Here, we showed that curcumin can improve the efficiency of gefitinib in the resistant NSCLC cells both in vitro and in vivo models.Methods/Principal FindingsAfter screening 598 herbal and natural compounds, we found curcumin could inhibit cell proliferation in different gefitinib-resistant NSCLC cell lines; concentration-dependently down-regulate EGFR phosphorylation through promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR. In addition, the anti-tumor activity of gefitinib was potentiated via curcumin through blocking EGFR activation and inducing apoptosis in gefitinib-resistant NSCLC cell lines; also the combined treatment with curcumin and gefitinib exhibited significant inhibition in the CL1-5, A549 and H1975 xenografts tumor growth in SCID mice through reducing EGFR, c-MET, cyclin D1 expression, and inducing apoptosis activation through caspases-8, 9 and PARP. Interestingly, we observed that the combined treatment group represented better survival rate and less intestinal mucosal damage compare to gefitinib-alone therapy. We showed that curcumin attenuated the gefitinib-induced cell proliferation inhibition and apoptosis through altering p38 mitogen-activated protein kinase (MAPK) activation in intestinal epithelia cell.Conclusions/SignificanceCurcumin potentiates antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC through inhibition of proliferation, EGFR phosphorylation, and induction EGFR ubiquitination and apoptosis. In addition, curcumin attenuates gefitinib-induced gastrointestinal adverse effects via altering p38 activation. These findings provide a novel treatment strategy that curcumin as an adjuvant to increase the spectrum of the usage of gefitinib and overcome the gefitinib inefficiency in NSCLC patients.

Despite good initial responses, drug resistance and disease recurrence remain major issues for lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations taking EGFR-tyrosine kinase inhibitors (TKI). To discover new strategies to overcome this issue, we investigated 40 essential oils from plants indigenous to Taiwan as alternative treatments for a wide range of illnesses. Here, we found that hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, exhibited potent anticancer effects. In this study, we demonstrated that hinokitiol inhibited the proliferation and colony formation ability of lung adenocarcinoma cells as well as the EGFR-TKI-resistant lines PC9-IR and H1975. Transcriptomic analysis and pathway prediction algorithms indicated that the main implicated pathways included DNA damage, autophagy, and cell cycle. Further investigations confirmed that in lung cancer cells, hinokitiol inhibited cell proliferation by inducing the p53-independent DNA damage response, autophagy (not apoptosis), S-phase cell cycle arrest, and senescence. Furthermore, hinokitiol inhibited the growth of xenograft tumors in association with DNA damage and autophagy but exhibited fewer effects on lung stromal fibroblasts. In summary, we demonstrated novel mechanisms by which hinokitiol, an essential oil extract, acted as a promising anticancer agent to overcome EGFR-TKI resistance in lung cancer cells via inducing DNA damage, autophagy, cell cycle arrest, and senescence in vitro and in vivo.

This study was aimed at investigating the antimelanogenic and antioxidative properties of the essential oil extracted from leaves of V. negundo Linn and the analysis of the chemical composition of this essential oil. The efficacy of the essential oil was evaluated spectrophotometrically, whereas the volatile chemical compounds in the essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). The results revealed that the essential oil effectively suppresses murine B16F10 tyrosinase activity and decreases the amount of melanin in a dose-dependent manner. Additionally, the essential oil significantly scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals, and showed potent reducing power versus metal-ion chelating properties in a dose-dependent pattern. The chemical constituents in the essential oil are sesquiterpenes (44.41%), monoterpenes (19.25%), esters (14.77%), alcohols (8.53%), aromatic compound (5.90%), ketone (4.96%), ethers (0.4%) that together account for 98.22% of its chemical composition. It is predicted that the aromatic compound in the essential oil may contribute to its antioxidant activities. The results indicated that essential oil extracted from V. negundo Linn leaves decreased melanin production in B16F10 melanoma cells and showed potent antioxidant activities. The essential oil can thereby serve as an inhibitor of melanin synthesis and could also act as a natural antioxidant.

The effects of added antioxidants on restructured combination (5050) beef-pork steaks were studied. Steaks were formulated to contain 20% fat and 0.75% salt. Antioxidants used at a 0.02% level (based on fat content of meat) were butylated hydroxyanisole (BHA), tertiary butyl hydroquinone (TBHQ), and a combination of BHA and TBHQ. Cooked steaks were evaluated for sensory properties and overall acceptability, initially and after 4, 8, 12, 16, an 20 wk of freezer storage. Steaks were also evaluated after the various storage times for 2-thiobarbituric acid (TBA) values, subjective color by panel evaluation, objective color with the Hunter color difference meter, tensile strength, shear value and cooking loss. Flavor and overall acceptability were significantly better in treated samples as compared to control samples. BHA was more effective in protecting color and TBHQ was more effective in protecting flavor (P

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Incorporation of surface-based capacitances (C/S) simulated by Helmholtz models with pore size distribution obtained from the non-local density functional theory precisely predicts the double-layer capacitance of distinct forms of carbon.

BackgroundMagnolia grandiflora L. flower is wildly used in Asian as a traditional herbal medication. The purpose of the study was to investigate the antimelanogenic and antioxidant properties of Magnolia grandiflora L. flower extract. In the study, the inhibitory effects of M. grandiflora L. flower extract on mushroom tyrosinase, B16F10 intracellular tyrosinase activity and melanin content were determined spectrophotometrically. Meanwhile, the antioxidative capacity of the flower extract was also investigated.ResultsOur results revealed that M. grandiflora L. flower extract inhibit mushroom tyrosinase activity (IC50 =11.1%; v/v), the flower extract also effectively suppressed intracellular tyrosinase activity (IC50 = 13.6%; v/v) and decreased the amount of melanin (IC50 = 25.6%; v/v) in a dose-dependent manner in B16F10 cells. Protein expression level of tyrosinase and tyrosinase-related protein 1 (TRP-1) were also decreased by the flower extract. Additionally, antioxidant capacities such as ABTS+ free radical scavenging activity, reducing capacity and total phenolic content of the flower extract were increased in a dose-dependent pattern.ConclusionsOur results concluded that M. grandiflora L. flower extract decreased the expression of tyrosinase and TRP-1, and then inhibited melanogenesis in B16F10 cells. The flower extract also show antioxidant capacities and depleted cellular reactive oxygen species (ROS). Hence, M. grandiflora L. flower extract could be applied as a type of dermatological whitening agent in skin care products.

The emergence and spread of antibiotic-resistant Neisseria gonorrhoeae has led to difficulties in treating patients, and novel strategies to prevent and treat this infection are urgently needed. Here, we examined 21 different nanomaterials for their potential activity against N. gonorrhoeae (ATCC 49226). Silver nanoparticles (Ag NPs, 120 nm) showed the greatest potency for reducing N. gonorrhoeae colony formation (MIC: 12.5 µg/ml) and possessed the dominant influence on the antibacterial activity with their properties of the nanoparticles within a concentration range that did not induce cytotoxicity in human fibroblasts or epithelial cells. Electron microscopy revealed that the Ag NPs significantly reduced bacterial cell membrane integrity. Furthermore, the use of clinical isolates of multidrug-resistant N. gonorrhoeae showed that combined treatment with 120 nm Ag NPs and cefmetazole produced additive effects. This is the first report to screen the effectiveness of nanomaterials against N. gonorrhoeae, and our results indicate that 120 nm Ag NPs deliver low levels of toxicity to human epithelial cells and could be used as an adjuvant with antibiotic therapy, either for topical use or as a coating for biomaterials, to prevent or treat multidrug-resistant N. gonorrhoeae.