Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U۹۳۷ 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 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: U۹۳۷ cells were cultured in RPMI ۱۶۴۰ with concentrations of ۲, ۴, ۶, ۸, and ۱۰ μM PTL for ۲۰-۲۴ hours for MTT assays. Apoptosis assays were performed with Annexin V-Alexa Fluor-۴۸۸/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 ۲-∆∆Ct method. The PTL–treated cells were stained with FITC-CD۳۸ antibody for flow cytometry analyses. Data were compared using one-way analysis of variance (ANOVA) by SPSS ۱۹. Results: Parthenolide inhibited growth of U۹۳۷ cells with IC۲۵ and IC۵۰ values of ۴ and ۵.۸ µM, respectively. Death induction with PTL was apoptotic. Flow cytometry showed a significant decrease in the percentage of CD۳۸+ U۹۳۷ cells in response to PTL. Osteopontin gene expression decreased in response to PTL. Conclusions: PTL induced apoptosis and reduced OPN gene expression in U۹۳۷ cells.

Keywords:

AML cell line U۹۳۷ , Osteopontin , Parthenolide