Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells
© 2016 Rungrojsakul et al. Background: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compou nd from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, W...
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th-cmuir.6653943832-418792017-09-28T04:23:54Z Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells Rungrojsakul M. Katekunlaphan T. Saiai A. Ampasavate C. Okonogi S. Sweeney C. Anuchapreeda S. © 2016 Rungrojsakul et al. Background: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compou nd 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. Methods: 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. Results: 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. Conclusion: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation. 2017-09-28T04:23:54Z 2017-09-28T04:23:54Z 2016-05-18 Journal 2-s2.0-84971325747 10.1186/s12906-016-1107-z https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84971325747&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/41879 |
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© 2016 Rungrojsakul et al. Background: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compou nd 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. Methods: 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. Results: 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. Conclusion: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation. |
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Rungrojsakul M. Katekunlaphan T. Saiai A. Ampasavate C. Okonogi S. Sweeney C. Anuchapreeda S. |
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Rungrojsakul M. Katekunlaphan T. Saiai A. Ampasavate C. Okonogi S. Sweeney C. Anuchapreeda S. Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
author_facet |
Rungrojsakul M. Katekunlaphan T. Saiai A. Ampasavate C. Okonogi S. Sweeney C. Anuchapreeda S. |
author_sort |
Rungrojsakul M. |
title |
Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
title_short |
Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
title_full |
Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
title_fullStr |
Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
title_full_unstemmed |
Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells |
title_sort |
down-regulatory mechanism of mammea e/bb from mammea siamensis seed extract on wilms' tumor 1 expression in k562 cells |
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2017 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84971325747&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/41879 |
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