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Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

ABSTRACT: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line.M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry.Treatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells.Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation.

SUBMITTER: Rungrojsakul M

PROVIDER: S-EPMC4870773 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

Rungrojsakul Methee M Katekunlaphan Trinnakorn T Saiai Aroonchai A Ampasavate Chadarat C Okonogi Siriporn S Sweeney Colleen A CA Anuchapreeda Songyot S

BMC complementary and alternative medicine 20160518

<h4>Background</h4>Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line.<h4>Methods</h4>M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. ...[more]

PMID: 27193767

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Project description:BackgroundThe emergence of antimalarial drug resistance encourages the search for new antimalarial agents. Mammea siamensis belongs to the Calophyllaceae family, which is a medicinal plant that is used in traditional Thai preparations. The hexane and dichloromethane extracts of this plant were found to have potent antimalarial activity. Therefore, this study aimed to isolate active compounds from M. siamensis flowers and evaluate their antimalarial potential and their interactions with Plasmodium falciparum lactate dehydrogenase (PfLDH).MethodsThe compounds from M. siamensis flowers were isolated by chromatographic techniques and evaluated for their antimalarial activity against chloroquine (CQ)-resistant P. falciparum (K1) strains using a parasite lactate dehydrogenase (pLDH) assay. Interactions between the isolated compounds and the PfLDH enzyme were investigated using a molecular docking method.ResultsThe isolation produced the following thirteen compounds: two terpenoids, lupeol (1) and a mixture of β-sitosterol and stigmasterol (5); two mammea coumarins, mammea A/AA cyclo D (6) and mammea A/AA cyclo F (7); and nine xanthones, 4,5-dihydroxy-3-methoxyxanthone (2), 4-hydroxyxanthone (3), 1,7-dihydroxyxanthone (4), 1,6-dihydroxyxanthone (8), 1-hydroxy-5,6,7-trimethoxyxanthone (9), 3,4,5-trihydroxyxanthone (10), 5-hydroxy-1-methoxyxanthone (11), 2-hydroxyxanthone (12), and 1,5-dihydroxy-6-methoxyxanthone (13). Compound 9 exhibited the most potent antimalarial activity with an IC50 value of 9.57 µM, followed by 10, 1, 2 and 13 with IC50 values of 15.48, 18.78, 20.96 and 22.27 µM, respectively. The molecular docking results indicated that 9, which exhibited the most potent activity, also had the best binding affinity to the PfLDH enzyme in terms of its low binding energy (-7.35 kcal/mol) and formed interactions with ARG109, ASN140, and ARG171.ConclusionThese findings revealed that isolated compounds from M. siamensis flowers exhibited antimalarial activity. The result suggests that 1-hydroxy-5,6,7-trimethoxyxanthone is a possible lead structure as a potent inhibitor of the PfLDH enzyme.

Project description:Seed-coat cracking and undesirable color of seed coat highly affects external appearance and commercial value of peanuts (Arachis hypogaea L.). With an objective to find genetic solution to the above problems, a peanut mutant with cracking and brown colored seed coat (testa) was identified from an EMS treated mutant population and designated as "peanut seed coat crack and brown color mutant line (pscb)." The seed coat weight of the mutant was almost twice of the wild type, and the germination time was significantly shorter than wild type. Further, the mutant had lower level of lignin, anthocyanin, proanthocyanidin content, and highly increased level of melanin content as compared to wild type. Using RNA-Seq, we examined the seed coat transcriptome in three stages of seed development in the wild type and the pscb mutant. The RNA-Seq analysis revealed presence of highly differentially expressed phenylpropanoid and flavonoid pathway genes in all the three seed development stages, especially at 40 days after flowering (DAF40). Also, the expression of polyphenol oxidases and peroxidase were found to be activated significantly especially in the late seed developmental stage. The genome-wide comparative study of the expression profiles revealed 62 differentially expressed genes common across all the three stages. By analyzing the expression patterns and the sequences of the common differentially expressed genes of the three stages, three candidate genes namely c36498_g1 (CCoAOMT1), c40902_g2 (kinesin), and c33560_g1 (MYB3) were identified responsible for seed-coat cracking and brown color phenotype. Therefore, this study not only provided candidate genes but also provided greater insights and molecular genetic control of peanut seed-coat cracking and color variation. The information generated in this study will facilitate further identification of causal gene and diagnostic markers for breeding improved peanut varieties with smooth and desirable seed coat color.

Project description:RationaleTumor necrosis factor-alpha (TNF-?) is a potent pro-inflammatory mediator and its expression is up-regulated in chronic obstructive pulmonary disease (COPD). Tristetraprolin (TTP) is implicated in regulation of TNF-? expression; however, whether TTP is involved in cigarette smoke-induced TNF-? expression has not been determined.MethodsTTP expression was examined by western blot analysis in murine alveolar macrophages and alveolar epithelial cells challenged without or with cigarette smoke extract (CSE). TNF-? mRNA stability, and the decay of TNF-? mRNA, were determined by real-time quantitative RT-PCR. TNF-? protein levels were examined at the same time in these cells. To identify the molecular mechanism involved, a construct expressing the human beta-globin reporter mRNA containing the TNF-? 3'-untranslated region was generated to characterize the TTP targeted site within TNF-? mRNA.ResultsCSE induced TTP down-regulation in alveolar macrophages and alveolar epithelial cells. Reduced TTP expression resulted in significantly increased TNF-? mRNA stability. Importantly, increased TNF-? mRNA stability due to impaired TTP function resulted in significantly increased TNF-? levels in these cells. Forced TTP expression abrogated the increased TNF-? mRNA stability and expression induced by CSE. By using the globin reporter construct containing TNF-? mRNA 3'-untranslated region, the data indicate that TTP directly targets the adenine- and uridine-rich region (ARE) of TNF-? mRNA and negatively regulates TNF-? expression at the post-transcriptional level.ConclusionThe data demonstrate that cigarette smoke exposure reduces TTP expression and impairs TTP function, resulting in significantly increased TNF-? mRNA stability and excessive TNF-? expression in alveolar macrophages and epithelial cells. The data suggest that TTP is a novel post-transcriptional regulator and limits excessive TNF-? expression and inflammatory response induced by cigarette smoke.

Project description:The present study explored the germination inhibitors present in the seeds of Capparis spinosa L., a plant species that is known for its ecological significance in preventing wind erosion and fixing sand in desertified areas. Additionally, its roots, leaves, and fruits possess medicinal properties, and are used to treat a range of ailments such as rheumatism, tumors, and diabetes. However, the plant's low germination rate under natural conditions is a major limitation. We aimed to improve the germination of C. spinosa seeds by investigating the effects of various infusions of caper seeds on the germination and seedling growth of Chinese cabbage seeds. A range of chemical reagents, hormonal immersions, and sand storage treatments were used to determine the differences in the germination rate of C. spinosa seeds. Our results revealed that among the various water extract concentrations tested, 100% water extract exhibited the strongest inhibitory effect on the germination and growth of the cabbage seeds, with a germination rate of (70.00 ± 0.09)%. Furthermore, the inhibitory effects on the germination and growth of cabbage seeds were found to be strongest when treated with the extract solution 1, yielding a germination rate of (83.33 ± 0.02)%. Notably, the leaves of Chinese cabbage seedlings turned yellow-green and yellow after treatment with the extract solution. These findings highlight the potential inhibitory effects of C. spinosa seed extracts on seed germination and growth and suggest that further research is needed to better understand the underlying mechanisms. The results of the germination experiment with methanol extract showed a sharp decline in the germination rate of Chinese cabbage seeds treated with 50% methanol extract, to (4.67 ± 0.02)%. These findings indicate the presence of germination-inhibiting substances in caper seeds. The highest germination potential was observed when the caper seeds were soaked in 30% PEG, reaching 35.00%. The highest germination rate, 19.33%, was observed when the seeds were soaked in 250 mg/L GA3 and 25 mmol/L NaCl. These results suggest that the germination inhibitor present in caper seeds affects the germination of cabbage seeds as well. The highest germination rate was achieved when the seeds were soaked with gibberellin. It is hoped that the research on the germination-inhibiting substances in caper seeds will provide a scientific foundation for improving and refining the artificial propagation and cultivation methods of this species.

Dataset Information

Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

Publications

Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

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