Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin

Background: Interfering with cell proliferation and survival is a critical role for antineoplastic drugs leading to cell death through induction of apoptosis. Alternative treatments with herbal extracts offer insights into acute myeloid leukemia (AML) therapy. Parthenolide (PTL), an extract from fev...

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Main Authors: Mahdi Zahedpanah, Mojgan Shaiegan, Seyed Hamidollah Ghaffari, Mohsen Nikbakht, Mahin Nikugoftar, Saeed Mohammadi
Format: Article
Language:English
Published: Varastegan Institute for Medical Sciences 2016-05-01
Series:Reports of Biochemistry and Molecular Biology
Subjects:
Online Access:http://rbmb.net/article-1-75-en.pdf
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author Mahdi Zahedpanah
Mojgan Shaiegan
Seyed Hamidollah Ghaffari
Mohsen Nikbakht
Mahin Nikugoftar
Saeed Mohammadi
author_facet Mahdi Zahedpanah
Mojgan Shaiegan
Seyed Hamidollah Ghaffari
Mohsen Nikbakht
Mahin Nikugoftar
Saeed Mohammadi
author_sort Mahdi Zahedpanah
collection DOAJ
description Background: Interfering with cell proliferation and survival is a critical role for antineoplastic drugs leading to cell death through induction of apoptosis. Alternative treatments with herbal extracts offer insights into acute myeloid leukemia (AML) therapy. Parthenolide (PTL), an extract from feverfew, induces apoptosis in primary human leukemia stem cells (LSCs) and bulk leukemic cell populations. Osteopontin (OPN) preserves cell viability in response to anticancer agents and its receptors could be utilized for therapeutic targeting of cancer cells. Methods: U937 cells were cultured in RPMI 1640 with concentrations of 2, 4, 6, 8, and 10 μM PTL for 20-24 hours for MTT assays. Apoptosis assays were performed with Annexin V-Alexa Fluor-488/PI as Annexin V+/PI- and Annexin V+/PI+ to measure early and late apoptosis, respectively. Quantitative real-time PCR was used to measure OPN gene expression using the 2-ΔΔCt method. The PTL–treated cells were stained with FITC-CD38 antibody for flow cytometry analyses. Data were compared using one-way analysis of variance (ANOVA) by SPSS 19. Results: Parthenolide inhibited growth of U937 cells with IC25 and IC50 values of 4 and 5.8 μM, respectively. Death induction with PTL was apoptotic. Flow cytometry showed a significant decrease in the percentage of CD38+ U937 cells in response to PTL. Osteopontin gene expression decreased in response to PTL. Conclusions: PTL induced apoptosis and reduced OPN gene expression in U937 cells.
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spelling doaj.art-db4c27b82ef245e9b818f10cad77abe62022-12-21T18:32:03ZengVarastegan Institute for Medical SciencesReports of Biochemistry and Molecular Biology2322-34802322-34802016-05-01428288Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in OsteopontinMahdi Zahedpanah0Mojgan Shaiegan1Seyed Hamidollah Ghaffari2Mohsen Nikbakht3Mahin Nikugoftar4Saeed Mohammadi5Blood Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranBlood Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Blood Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranBlood Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranBackground: Interfering with cell proliferation and survival is a critical role for antineoplastic drugs leading to cell death through induction of apoptosis. Alternative treatments with herbal extracts offer insights into acute myeloid leukemia (AML) therapy. Parthenolide (PTL), an extract from feverfew, induces apoptosis in primary human leukemia stem cells (LSCs) and bulk leukemic cell populations. Osteopontin (OPN) preserves cell viability in response to anticancer agents and its receptors could be utilized for therapeutic targeting of cancer cells. Methods: U937 cells were cultured in RPMI 1640 with concentrations of 2, 4, 6, 8, and 10 μM PTL for 20-24 hours for MTT assays. Apoptosis assays were performed with Annexin V-Alexa Fluor-488/PI as Annexin V+/PI- and Annexin V+/PI+ to measure early and late apoptosis, respectively. Quantitative real-time PCR was used to measure OPN gene expression using the 2-ΔΔCt method. The PTL–treated cells were stained with FITC-CD38 antibody for flow cytometry analyses. Data were compared using one-way analysis of variance (ANOVA) by SPSS 19. Results: Parthenolide inhibited growth of U937 cells with IC25 and IC50 values of 4 and 5.8 μM, respectively. Death induction with PTL was apoptotic. Flow cytometry showed a significant decrease in the percentage of CD38+ U937 cells in response to PTL. Osteopontin gene expression decreased in response to PTL. Conclusions: PTL induced apoptosis and reduced OPN gene expression in U937 cells.http://rbmb.net/article-1-75-en.pdfAML cell line U937OsteopontinParthenolide
spellingShingle Mahdi Zahedpanah
Mojgan Shaiegan
Seyed Hamidollah Ghaffari
Mohsen Nikbakht
Mahin Nikugoftar
Saeed Mohammadi
Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
Reports of Biochemistry and Molecular Biology
AML cell line U937
Osteopontin
Parthenolide
title Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
title_full Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
title_fullStr Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
title_full_unstemmed Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
title_short Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin
title_sort parthenolide induces apoptosis in committed progenitor aml cell line u937 via reduction in osteopontin
topic AML cell line U937
Osteopontin
Parthenolide
url http://rbmb.net/article-1-75-en.pdf
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