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Title: A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines

Abstract

Highlights: {yields} 2,6-Diisopropylphenyl-docosahexaenoamide conjugates (DIP-DHA) inhibits the proliferation of T-cell leukemic cell lines. {yields} DIP-DHA resulted in increased activation of caspase-3, and caspase-7. {yields} DIP-DHA significantly downregulated CXCR4 surface expression. -- Abstract: We have previously characterized the effects of 2,6-diisopropylphenyl-docosahexaenoamide (DIP-DHA) conjugates and their analogs on the proliferation and progression of breast cancer cell lines. For this study, we investigated the effects of the DIP-DHA conjugate on 2 representative T cell acute lymphoblastic leukemia (T-ALL) cell lines: CEM and Jurkat. Treatment of both cell lines with DIP-DHA resulted in significantly greater inhibition of proliferation and induction of apoptosis than that of parent compounds, 2,6-diisopropylphenol (DIP) or docosahexaenoate (DHA). Treatment of the cells with DIP-DHA resulted in increased activation of caspase-3, and caspase-7. Furthermore, induction of apoptosis in both cell lines was reversed in the presence of a caspase family inhibitor. Treatment with DIP-DHA reduced mitochondrial membrane potential. These observations suggest that the effects are driven by intrinsic apoptotic pathways. DIP-DHA treatment also downregulated surface CXCR4 expression, an important chemokine receptor involved in cancer metastasis that is highly expressed in both CEM and Jurkat cells. In conclusion, our data suggest that the DIP-DHA conjugate exhibits significantly more potent effects on CEMmore » and Jurkat cells than that of DIP or DHA alone. These conjugates have potential use for treatment of patients with T cell acute lymphoblastic leukemia.« less

Authors:
; ; ;  [1];  [1];  [2];  [2]
  1. Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22207414
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 411; Journal Issue: 2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL PROLIFERATION; GENE REGULATION; LEUKEMIA; MAMMARY GLANDS; METASTASES; MITOCHONDRIA; PATIENTS; RECEPTORS

Citation Formats

Altenburg, Jeffrey D., Harvey, Kevin A., McCray, Sharon, Xu, Zhidong, Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org, Department of Biology, Indiana University-Purdue University, Indianapolis, IN, and Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.06.172.
Altenburg, Jeffrey D., Harvey, Kevin A., McCray, Sharon, Xu, Zhidong, Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org, Department of Biology, Indiana University-Purdue University, Indianapolis, IN, & Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines. United States. doi:10.1016/J.BBRC.2011.06.172.
Altenburg, Jeffrey D., Harvey, Kevin A., McCray, Sharon, Xu, Zhidong, Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org, Department of Biology, Indiana University-Purdue University, Indianapolis, IN, and Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. Fri . "A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines". United States. doi:10.1016/J.BBRC.2011.06.172.
@article{osti_22207414,
title = {A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines},
author = {Altenburg, Jeffrey D. and Harvey, Kevin A. and McCray, Sharon and Xu, Zhidong and Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org and Department of Biology, Indiana University-Purdue University, Indianapolis, IN and Department of Medicine, Indiana University School of Medicine, Indianapolis, IN},
abstractNote = {Highlights: {yields} 2,6-Diisopropylphenyl-docosahexaenoamide conjugates (DIP-DHA) inhibits the proliferation of T-cell leukemic cell lines. {yields} DIP-DHA resulted in increased activation of caspase-3, and caspase-7. {yields} DIP-DHA significantly downregulated CXCR4 surface expression. -- Abstract: We have previously characterized the effects of 2,6-diisopropylphenyl-docosahexaenoamide (DIP-DHA) conjugates and their analogs on the proliferation and progression of breast cancer cell lines. For this study, we investigated the effects of the DIP-DHA conjugate on 2 representative T cell acute lymphoblastic leukemia (T-ALL) cell lines: CEM and Jurkat. Treatment of both cell lines with DIP-DHA resulted in significantly greater inhibition of proliferation and induction of apoptosis than that of parent compounds, 2,6-diisopropylphenol (DIP) or docosahexaenoate (DHA). Treatment of the cells with DIP-DHA resulted in increased activation of caspase-3, and caspase-7. Furthermore, induction of apoptosis in both cell lines was reversed in the presence of a caspase family inhibitor. Treatment with DIP-DHA reduced mitochondrial membrane potential. These observations suggest that the effects are driven by intrinsic apoptotic pathways. DIP-DHA treatment also downregulated surface CXCR4 expression, an important chemokine receptor involved in cancer metastasis that is highly expressed in both CEM and Jurkat cells. In conclusion, our data suggest that the DIP-DHA conjugate exhibits significantly more potent effects on CEM and Jurkat cells than that of DIP or DHA alone. These conjugates have potential use for treatment of patients with T cell acute lymphoblastic leukemia.},
doi = {10.1016/J.BBRC.2011.06.172},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 411,
place = {United States},
year = {2011},
month = {7}
}