Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo

Purpose Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. Methods We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. Results CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. Conclusion We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer (AU)

Anti-proliferative effects of paeonol on human prostate cancer cell lines DU145 and PC-3

Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway (AU)

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Reactive oxygen species derived from NAD(P)H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries

Chronic ethanol consumption is a risk factor for cardiovascular diseases. We studied whether NAD(P)H oxidase-derived reactive oxygen species (ROS) play a role in ethanol-induced hypertension, vascular dysfunction, and protein expression in resistance arteries. Male Wistar rats were treated with ethanol (20 % v/v) for 6 weeks. Ethanol treatment increased blood pressure and decreased acetylcholine-induced relaxation in the rat mesenteric arterial bed (MAB). These responses were attenuated by apocynin (30 mg/kg/day; p.o. gavage). Ethanol consumption increased superoxide anion (O2−) generation and decreased nitrate/nitrite (NOx) concentration in the rat MAB and apocynin prevented these responses. Conversely, ethanol did not affect the concentration of hydrogen peroxide (H2O2) and reduced glutathione (GSH) or the activity of superoxide dismutase (SOD) and catalase (CAT) in the rat MAB. Ethanol increased interleukin (IL)-10 levels in the rat MAB but did not affect the levels of tumor necrosis factor (TNF)-α, IL-6, or IL-1β. Ethanol increased the expression of Nox2 and the phosphorylation of SAPK/JNK, but reduced eNOS expression in the rat MAB. Apocynin prevented these responses. However, ethanol treatment did not affect the expression of Nox1, Nox4, p38MAPK, ERK1/2, or SAPK/JNK in the rat MAB. Ethanol increased plasma levels of TBARS, TNF-α, IL-6, IL-1β, and IL-10, whereas it decreased NOx levels. The major finding of our study is that NAD(P)H oxidase-derived ROS play a role on ethanol-induced hypertension and endothelial dysfunction in resistance arteries. Moreover, ethanol consumption affects the expression and phosphorylation of proteins that regulate vascular function and NAD(P)H oxidase-derived ROS play a role in such responses (AU)

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Role of acetosyringone in the accumulation of a set of RNAs in the arbuscular mycorrhiza fungus Glomus intraradices

Plant root exudates contain a range of low molecular weight metabolites that trigger many of the structural and physiological changes associated with the progression and establishment of mycorrhizal symbiosis. Here, the physiological response triggered by acetosyringone (AS) was studied in Glomus intraradices. Incubation of G. intraradices spores with AS resulted in an overall increase in hyphal respiration. A G. intraradices cDNA library was then screened with a total cDNA probe obtained from the AS-treated spores and mycelium. cDNAs from genes induced in AS-treated G. intraradices were assigned to different functional categories, such as protein synthesis, membrane transport, signal transduction, and general metabolism, but without further information regarding their function or identity. A cDNA coding a fragment of a histidine kinase was also induced by AS, suggesting a two-component mediated response to the metabolite. In addition, the differential accumulation of a cruciform DNA-binding protein mRNA, termed as GiBP1, was also observed. Time-course experiments demonstrated the rapid accumulation of GiBP1 within 2 h of AS induction. These results indicate the presence of a set of fungal genes that are induced by AS. These findings are discussed in terms of the possible molecular events that follow the exchange of signals between mycorrhizal symbionts (AU)

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Helichrysum italicum, una planta mediterránea con potencial terapéutico / Helichrysum italicum, a mediterr enean plant with therapeutic potential

Helichrysum italicum es una especie vegetal de distribución en toda el área mediterránea y con amplio uso popular como expectorante, colerética, antiasmática y antiinflamatoria. Aunque no está recogida en ningún formulario ni farmacopea oficial, sí aparecen otras especies relacionadas y con efectos similares, como H. arenarium. Entre los estudios realizados con extractos o principios de H. italicum, destacan por su interés las propiedades antiinflamatorias y antiinfecciosas. Los compuestos aislados más característicos son los flavonoides, acetofenonas, floroglucinoles y )-pironas, conjuntamente con el aceite esencial. Varios de los principios más relevantes aislados han sido objeto de profundos estudios farmacológicos, destacando las propiedades antiinflamatorias y antioxidantes de gnafaliína, tilirósido y pinocembrina, y las propiedades antiinflamatorias de diversos acetofenonas, especialmente el inhibidor dual del metabolismo de ácido araquidónico y de la peroxidación lipídica, identificado como 4-hidroxi-3-(3-metil-2-butenil)-acetofenona.(AU)

Helichrysum italicumis a medicinal plant found all around the Mediterranean area and used in folk medicine as an expectorant and choleretic, as well as an anti-asthmatic and anti-inflammatory agent. Although it does not appear in any official compendium or pharmacopoeia, other closely related species with similar properties do, such as H. arenarium. Among the pharmacological properties of the extracts and compounds isolated from H. italicum, the most relevant are its anti-inflammatory and anti-infectious properties. The most characteristic natural products isolated from this plant are flavonoids, acetophenones, phloroglucinols and )-pyrones, together with its essential oil. Several of these substances have been subjected to pharmacological studies; thus, the anti-inflammatory and anti-oxidant properties of gnafaliin, pinocembrin and tiliroside have been reported as well as the anti-inflammatory activity of the acetophenones, especially the dual inhibitor of the arachidonic acid metabolism, identified as 4-hydroxy-3-(3-methyl-2-butenyl)-acetophenone (AU)