Showing papers on "Brucine published in 2019"

Brucine Suppresses Vasculogenic Mimicry in Human Triple-Negative Breast Cancer Cell Line MDA-MB-231.

Abstract: Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β-catenin signaling pathway.

Abstract: Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.

Dielectric spectroscopic studies in supercooled liquid and glassy states of Acemetacin, Brucine and Colchicine

Abstract: The physical and chemical instability of amorphous pharmaceuticals during storage has become a major problem for the pharmaceutical industry, as most of the pharmaceuticals including some life saving drugs are also found to be poorly water soluble. Molecular mobility is a key factor to understand the various crucial parameters that determine the stability of amorphous phase. The molecular dynamics in the supercooled liquid and glassy states of three Active Pharmaceutical Ingredients (API) Acemetacin, Brucine and Colchicine were characterized by molecular relaxation (mobility) using broadband dielectric spectroscopy (BDS) in a wide frequency range. Primary structural relaxation and intra-molecular (non Johari-Goldstein) secondary relaxation were observed above and below Tg respectively in all three title compounds. The dielectric spectra were fitted to the Havriliak-Negami (HN) function. The temperature dependence of the structural relaxation time followed Vogel-Fulcher-Tamman (VFT) equation and the secondary relaxation followed Arrhenius equation. By Coupling model (CM) prediction, the secondary relaxations in all title compounds were found to be non JG. The width of the structural relaxation peak decreases with temperature for brucine and colchicine while it increases for acemetacin. By Differential Scanning Calorimetry (DSC) experiment, we confirmed that the selelcted compounds are good glass formers and their structural properties and hydrogen bonding were studied by Fourier Transform Infrared spectroscopy (FTIR) and verified by Density Functional theory (DFT). By BDS, the parameters which describe the molecular dynamics in the supercooled and glassy states of the title compounds, like glass transition temperature (Tg) the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times (τα), the fragility (m) and the activation energy of the secondary relaxation (Ea-γ), were determined. The higher values of Tg determined (307.9 K for acemetacin, 366.2 K for brucine and 374.5 K for colchicine) indicates stability of their amorphous phase at normal storage conditions. The fragility index values of the title compounds indicate intermediately fragile behaviour. The FTIR analysis of the crystalline and amorphous states of brucine, acemetacin and colchicine shows the presence of hydrogen bonding in amorphous phase of the title compounds and verified that their molecular structures were retained in the amorphous state.

Brucine inhibits TNF-α-induced HFLS-RA cell proliferation by activating the JNK signaling pathway.

Abstract: Rheumatoid arthritis (RA) is a diffuse connective tissue disease. Brucine selectively inhibits cell immunity, immune hypersensitivity and induces apoptosis. The current study aimed to investigate effects of brucine on human fibroblast-like synoviocytes (HFLS) of RA and to clarify associated molecular mechanisms. HFLS-RA were treated with tumor necrosis factor (TNF)-α prior to treatment with brucine at carrying concentrations. Cell Counting Kit-8 assays were performed to evaluate HFLS-RA proliferation. Western blot assays were employed to examine c-Jun N-terminal kinase (JNK) expression and phosphorylation in TNF-α-induced HFLS-RA. An association between brucine treatment and JNK phosphorylation was assessed by employing a linear regression analysis. The results suggested that low doses of brucine (0.125 and 0.25 mg/ml) significantly reversed proliferation effects induced by TNF-α, however, final cell viabilities were increased compared with the untreated control (P>0.05 and P 0.05). Brucine treatment significantly decreased JNK phosphorylation compared with the TNF-α group (P<0.05). JNK specific inhibitor, SP600125, significantly inhibited brucine-induced cell viability enhancement compared with the brucine-treated groups without inhibitor (P<0.05). A linear regression analysis suggested that brucine was associated with JNK phosphorylation in TNF-α-treated HFLS-RA. In conclusion, brucine significantly inhibited TNF-α-induced HFLS-RA proliferation by activating the JNK signaling pathway. Therefore, brucine may have potential clinical applications in the treatment of RA.

Biochemical studies evaluating the chemopreventive potential of brucine in chemically induced mammary carcinogenesis of rats.

Abstract: The present study was aimed to investigate the dose dependent chemopreventive activity of brucine against 7, 12-dimethylbenz (a) anthracene induced mammary gland tumorigenesis in rats. The mammary ...

An analytical strategy for the identification of carbamates, toxic alkaloids, phenobarbital and warfarin in stomach contents from suspected poisoned animals by thin-layer chromatography/ultraviolet detection.

Abstract: In this study, an analytical strategy to identify brucine, strychnine, methomyl, carbofuran (alkaline compounds), phenobarbital, and warfarin (acid compounds) using thin-layer chromatography (TLC) ...

Brucine soluble microneedle, preparation method, detection method and application

Abstract: The invention relates to a brucine soluble microneedle. The microneedle is composed of 0.012002-0.012010 parts of brucine, 0.998-1.006 parts of chondroitin sulfate and 0.997-1.005 parts of polyvinylpyrrolidone. According to the brucine soluble microneedle in the invention, the soluble microneedle is prepared by using a vacuum pressure reduction method, the content of the brucine in the sample andthe in-vitro transdermal effect are determined by adopting a high performance liquid chromatography method, the prepared brucine soluble microneedle has good morphology and mechanical property, thereby solving the problem that the medicine is difficult to permeate into the stratum corneum, and solving the problem that the effective dosage of the brucine in treating rheumatoid arthritis diseases isvery close to the poisoning dosage, so that the clinical application of the brucine is severely limited; the brucine soluble microneedle prepared by the invention can be used for remarkably reducingepithelial hyperplasia and cartilage erosion of the synovial membrane of the ankle joint part and maintaining the joint gap; a good treatment effect on the rat RA is achieved; and the established brucine content determination method is simple, accurate, and high in feasibility.