Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells

BACKGROUND: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by ionizing radiation (IR). Protein kinase CK2 is a constitutively active serine/threonine kinase which plays a vital role in cell proliferation and inflammation. In this study, we investigated the potential role of CK2 in PVRN after IR exposure. RESULT: Specific CK2 inhibitors, Quinalizarin and CX-4945, were employed to effectively suppressed the kinase activity of CK2 in human umbilical vein endothelial cells (HUVECs) without affecting their viability. Results showing that conditioned medium from IR-exposed HUVECs increased cell viability of A549 and H460 cells, and the pretreatment of CK2 inhibitors slowed down such increment. The secretion of IL-8 and IL-6 in HUVECs was induced after exposure with IR, but significantly inhibited by the addition of CK2 inhibitors. Furthermore, IR exposure elevated the nuclear phosphorylated factor-κB (NF-κB) p65 expression in HUVECs, which was a master factor regulating cytokine production. But when pretreated with CK2 inhibitors, such elevation was significantly suppressed. CONCLUSION: This study indicated that protein kinase CK2 is involved in the key process of the IR induced perivascular resistant niche, namely cytokine production, by endothelial cells, which finally led to radioresistance of non-small cell lung cancer cells. Thus, the inhibition of CK2 may be a promising way to improve the outcomes of radiation in nonsmall cell lung cancer cells.

Potential of natural repellents methylanthranilate and anthraquinone applied on maize seeds and seedlings against house sparrow (Passer domesticus) in captivity / Potencial de repelentes naturais, metilantranilato e antraquinona aplicados em sementes de milho e mudas contra o pardal (Passer domesticus) em cativeiro

Abstract Various bird pests caused severe economic losses to valuable crops and fruit orchards all over the world. Among the birds, house sparrow is also considered to cause heavy plunder, not only to seeds of crops but also seedlings especially in organic farming. In present study two bird repellents, methylanthranilate and anthraquinone tested against house sparrows on maize seeds and seedlings in aviary conditions. Trial group in aviary-I, the treated maize seeds and seedlings with different doses of both bird repellents, control group in aviary-II, untreated seeds and seedlings were provided for three hours in the early morning. In each aviary, two closed circuit cameras were also installed to monitor the behavioral responses against different concentrations of both chemical repellents. Statistical analysis showed that there existed highly significant (P<0.01) variations among the trial and control groups for seeds and seedlings. By comparing both repellents, significant (P<0.05) differences were detected and anthraquinone showed better efficacy when compared to methylanthranilate, but in maize seedlings both repellents equal repellent properties. Non-significant (P>0.05) differences were observed in different grading of both natural chemical repellents for maize seeds while significant (P<0.05) variations were noticed for maize seedlings when provided to sparrows. By videotaped behavior sparrows presented manifest head juddering and feather upsetting activities by consumption of treated seeds and seedlings with higher concentrations of both natural bird repellents.

Resumo Várias pragas de aves causaram graves perdas econômicas para cultivos valiosos e pomares de frutas em todo o mundo. Entre os pássaros, o pardal da casa também é considerado um grande saqueo, não só para as sementes das culturas, mas também para as mudas, especialmente na agricultura orgânica. No presente estudo, dois repelentes de aves, metilantranilato e antraquinona testados contra pardais de casa em sementes de milho e mudas em condições de aviário. O grupo de ensaio em aviary-I, as sementes de milho tratadas e as mudas com diferentes doses de repelentes de aves, grupo de controle em aviary-II, sementes não tratadas e mudas foram fornecidas por três horas no início da manhã. Em cada aviário, duas câmeras de circuito fechado também foram instaladas para monitorar as respostas comportamentais contra diferentes concentrações de ambos os repelentes químicos. A análise estatística mostrou que existiam variações altamente significativas (P<0,01) entre os grupos de teste e controle para sementes e mudas. Ao comparar os dois repelentes, detectaram-se diferenças significativas (P<0,05) e a antraquinona apresentou maior eficácia quando comparada ao metilantranilato, mas em mudas de milho, ambos os repelentes são iguais às propriedades repelentes. As diferenças não significantes (P>0,05) foram observadas em diferentes classificações de repelentes químicos naturais para sementes de milho, enquanto as variações significativas (P<0,05) foram observadas para as mudas de milho quando fornecidas aos pardais. Por um comportamento gravado em video, os pardais apresentaram manifestações de cabeça e vibrações de penas por consumo de sementes tratadas e mudas com maiores concentrações de repelentes de aves naturais.

Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM) for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

Revisión bibliográfica sobre la composición química y actividades farmacológicas del género Vismia (Guttiferae) / A review on the chemical composition and pharmacological activities of Vismia genus (Guttiferae)

Vismia genus is an important source of natural medicinal products, thus, information collected in this review is an attempt to cover the most recent developments in the ethnopharmacology, pharmacology and phytochemistry of this genus. Anthraquinones and other quinonoid derivates, terpenoids and volatile constituents have been reported as the major constituents isolated from different Vismia species. On the other hand, pharmacological studies carried out to date have revealed the variety of anti-plasmodium, antioxidant, antimicrobial and antifungical properties of extracts and pure isolated compounds of the different species tested. The information summarized in this paper intends to serve as a reference tool to practitioners in the fields of etnopharmacology and chemistry of natural products.

El género Vismia es una fuente importante de productos naturales medicinales, es por esto que la información reunida en la presente revisión cubre los estudios más recientes en la etnofarmacología, farmacología y fitoquímica de este género. Antraquinonas y otros derivados quinoides, terpenos y constituyentes volátiles han sido reportados como los compuestos mayormente aislados de las diferentes especies de Vismia. Por otro lado, los estudios farmacológicos realizados hasta los momentos muestran las diversas propiedades antiplasmodicas, antioxidantes, antimicrobianas y antifúngicas que presentan tanto los extractos como los compuestos puros aislados de las diferentes especies ensayadas. La información resumida en este documento intenta servir de material de apoyo para investigadores en los campos de la etnofarmacologia y la química de productos naturales.

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice.

Naturally occurring plant products belonging to different chemical classes namely alizarin, an anthraquinone, caffeine, a methylxanthine derivative and quercetin, a flavonol were studied for their effect on elimination of metabolites of [14C]-N-nitrosodiethylamine (14C-NDEA) through respiration in mice. Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 microg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism. Radioactive CO2 exhaled in 60 min increased by 2, 1.61 and 1.4-folds in animals treated with caffeine, quercetin and alizarin for 8 weeks respectively. This increase in exhalation in caffeine-treated animals was achieved even in 2 weeks. These compounds had no adverse effects on the absorption of radioactive NDEA from the gut of the animals as shape and time of 14CO2 peak was similar in i.p. and orally administered [14C-NDEA]. Increased detoxification/elimination of the carcinogen could be one of the mechanisms for the anticarcinogenic properties of these phytochemicals in lung tumorigenesis induced by orally administered NDEA.

Comparison of the antioxidant action of the alcoholic extract of Rubia cordifolia with rubiadin.

The inhibition of FeSO4 induced lipid peroxidation in rat liver by alcoholic extract of Rubia cordifolia and by one of its constituent rubiadin (1, 3-dihydroxy-2-methyl anthraquinone) (pure form) has been compared. Both have been found to inhibit lipid peroxidation in a dose dependent manner. Whereas the former shows both oxidising and reducing properties with Fe2+ and Fe3+, the latter shows oxidising property only by converting Fe2+ to Fe3+. The former inhibits the oxidation of reduced glutathione while the latter does not.

Effect of mycotoxins isolated from Penicillium nigricans on glucose-6-phosphate dehydrogenase.

A new mycotoxin product (NMP) was isolated from the culture of mutated wild strain of P. nigricans which is less toxic and has sterol derivative. NMP (LD50 > 1 g/kg) showed antimicrobial and antineoplastic activities and does not affect the hematological parameters like RBC count and hemoglobin. It maintained normal blood glucose level by increasing the enzyme activity of glucose-6-phosphate dehydrogenase (EC-1.1.1.49; G-6-PDH) by 30%. It also maintained the normal ion balance in the blood of mice. NMP decreased Km value of glucose-6-phosphate dehydrogenase and thus increased substrate affinity of the enzyme. Reduction of toxicity of NMP has been well explained by higher activity of G-6-PDH which is highly specific for production of NADPH.

Anticestodal principles of nigella sativa, linn. [kalonji] seeds

Efficacy of the total glycosides, saponins and anthraquinones isolated from Nigella sativa [Kalonji] seeds was Judged in the goats infected naturally with mixed gastro-intestinal nematodes. The glycosides were administered orally to groups of sheep in 100, 150 and 200 mg/kg body weight doses. Nilzan ' 15 ml/15 kg was similarly administered to the control sheep. Pre - and post - treatment faecal eggs per gram [EPG] counts and their percentage reductions were determined on 3rd,10th and 15th day of drug administration. Their 100, 150 and 200 mg/kg oral dose of the glycosides reduced the EPC counts highly significantly [P<0.001] on day 10 and15. Statistically 150 and 200mg/kg dose of N. sativa glycosides were as effective as Nilzan ' against goat cestodes on post-treatment days 10 day 15. However, a lower dose of 100 mg /kg of the glycosides could also produce results similar to Nilzan ' on and 15 only. The saponins and anthraquinones isolated from the N. sativa seeds, however, failed to exert any significant effect in their 100, 200 and 300 mg/kg doses. These data suggest that the total glycosides of N. sativa seeds possess considerable activity against cestodes in the goats and may be responsible for the Anticestodal efficacy of the powdered seeds already reported to be effective against tape worms of shep

Antimicrobial activities of mycotoxin MT81 and its structural derivatives.

Antimicrobial activities of mycotoxin MT81 and its acetylated, benzoylated and acetic acid derivatives were determined by zone inhibition method. MT81, acetylated MT81 and acetic acid MT81 exhibited sensitivity (31.25, 62.50, 62.50 micrograms/ml respectively) to all the test bacteria. Benzoylated-MT81 did not exhibit any activity even up to 1000 mcg/ml. MT81, its acetylated and acetic acid derivatives exhibited antifungal activity up to 62.5 micrograms/ml and 125.0 micrograms/ml respectively against test yeasts and other fungi. Benzoylated MT81 also exhibited antifungal activity but the degree was comparatively less.

Estudio comparativo de las hojas y extractos de aloe arborescens y aloe barbadensis: parte I: actividad cicratizante y compuestos antraquinónicos / Comparative study of leaves and extracts of aloe arborescens and aloe barbadensis: part I: Realing activity and anthroquinone compounds

Se exponen los resultados del estudio farmacológico, resultado del estudio comparativo por cromatografía en capa delgada de los componentes antraquinónicos presentes en las hojas de Aloe arborescens y Aloe barbadensis. Los componentes antraquinónicos fueron determinados cuantitativamente por el método colorimétrico. Los extractos elaborados de hojas frescas de ambas especies cultivadas en Cuba mostraron una buena actividad bioestimulante de cicatrización