The 170 kDa plasma membrane P-glycoprotein (Pgp) causes the efflux of chemotherapeutic drugs from cells and is believed to be an important mechanism in multidrug resistance (MDR) in human cancer. This study demonstrates that some putative flavonoids, i.e., flavonols (quercetin and kaempferol) and isoflavones (genistein and daidzein) markedly increase the sensitivity of the multidrug-resistant human cervical carcinoma KB-V1 cells (high Pgp expression) to vinblastine and paclitaxel dose-dependently, and also decrease the relative resistance of these anti-cancer-drugs in KB-V1 cells. None of the flavonoids had a significant effect on vinblastine and paclitaxel cytotoxicity in wildtype drug-sensitive KB-3-1 cells (lacking Pgp). These flavonoids also caused an increase in intracellular accumulation, and reduced the efflux of Rh123 and 3[H]vinblastine in KB-V1 cells, but not in KB-3-1 cells. The flavonols increased the inhibitory effectiveness of Pgp activity in MDR KB-V1 cells more than isoflavones. Only treatment with flavonols up to 48 h was able to significantly decrease the Pgp expression in a dose-dependent manner in KB-V1 cells. These findings provide evidence that flavonols reduced Pgp expression and function resulting in the inhibition of Pgp activity, but isoflavones modulated intracellular drug levels by inhibiting Pgp function with no effect on Pgp expression. Among the flavonoids tested, flavonols, particularly kaempferol, exhibit the most potent MDR reversing property in KB-V1 cells.
BackgroundZearalenone (ZEA) is a phytoestrogen from Fusarium species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.MethodsCell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.ResultsZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only ERp29 mRNA transcript increased.ConclusionZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.
Catheter-related infections (CRIs) are associated with the formation of pathogenic biofilms on the surfaces of silicone catheters, which are ubiquitous in medicine. These biofilms provide protection against antimicrobial agents and facilitate the development of bacterial resistance to antibiotics. The application of photothermal agents on catheter surfaces is an innovative approach to overcoming biofilm-generated CRIs. Gold nanoshells (AuNSs) represent a promising photothermal tool, because they can be used to generate heat upon exposure to near-infrared (NIR) radiation, are biologically inert at physiological temperatures, and can be engineered for the photothermal ablation of cells and tissue. In this study, AuNSs functionalized with carboxylate-terminated organosulfur ligands were attached to model catheter surfaces and tested for their effectiveness at killing adhered Enterococcus faecalis (E. faecalis) bacteria. The morphology of the AuNSs was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), while the elemental composition was characterized by energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). Furthermore, optical and photothermal properties were acquired by ultraviolet-visible (UV-vis) spectroscopy and thermographic imaging with an infrared camera, respectively. Bacterial survival studies on AuNS-modified surfaces irradiated with and without NIR light were evaluated using a colony-formation assay. These studies demonstrated that AuNS-modified surfaces, when illuminated with NIR light, can effectively kill E. faecalis on silicone surfaces.
The leaf extracts from bitter melon were able to reverse the MDR phenotype, which is consistent with an increase in intracellular accumulation of the drug. The exact nature of the active components of bitter melon leaf extracts remains to be identified.
The objective of this study was to investigate the in vitro bioactivities associated with the content of phytochemicals in the extracts from perilla seed meal extract (PSME) compared with dietary seed (PSE). PSE had higher total phenolics and flavonoids content than PSME. However, hydrophilic phytochemical contents in PSME were quantitatively equivalent to PSE. Rosmarinic acid was predominantly found in both extracts. Cell viability and anti‐mutagenicity testing demonstrated that PSE and PSME were biosecured and non‐genotoxic. Both extracts strongly scavenged free radicals and significantly reduced reactive oxygen species (ROS) production. The extracts drastically diminished nitric oxide (NO) production of LPS‐treated RAW 264.7 cells via iNOS mRNA expression. The expression of IL‐6 and COX‐2 were evidently inhibited by these extracts. It could be concluded that PSE and PSME clearly showed in vitro anti‐mutagenicity, antioxidant and anti‐inflammatory capacities. In particular, the by‐product perilla seed meal could be considered as a high nutritive functional food. Practical applications This study suggests that the seed meals, a by‐product from seed oil industry, can be utilized as a valuable dietary source for humans and animals. The high content of polyphenols and their bioactivities can be developed as functional foods, and excipients and fillers in pharmaceuticals and nutraceuticals production. Moreover, recycling of the by‐product seed meals should also reduce environmental and sanitary pollution.
Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1β, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.
Core@shell metal nanoparticles have emerged as promising photocatalysts because of their strong and tunable plasmonic properties; however, marked improvements in photocatalytic efficiency are needed if these materials are to be widely used in practical applications. Accordingly, the design of new and functional light-responsive nanostructures remains a central focus of nanomaterial research. To this end, we report the synthesis of nanorattles comprising hollow gold–silver nanoshells encapsulated within vacuous tin oxide shells of adjustable thicknesses (∼10 and ∼30 nm for the two examples prepared in this initial report). These composite nanorattles exhibited broad tunable optical extinctions ranging from ultraviolet to near-infrared spectral regions (i.e., 300–745 nm). Zeta potential measurements showed a large negative surface charge of approximately −35 mV, which afforded colloidal stability to the nanorattles in aqueous solution. We also characterized the nanorattles structurally and compositionally using scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Futhermore, finite-difference time-domain simulation and photoluminescence properties of the composited nanoparticles were investigated. Collectively, these studies indicate that our tin oxide-coated hollow gold–silver nanorattles are promising candidates for use in solar-driven applications.
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