alexa EDL-360: A Potential Novel Antiglioma Agent
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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Review Article

EDL-360: A Potential Novel Antiglioma Agent

Amira Hosni-Ahmed1,2,6*, Michelle Sims1,2, Terreia S Jones4, Renukadevi Patil3, Shivaputra Patil3, Hossam Abdelsamed5,6, Charles R. Yates3, Duane D Miller3 and Lawrence M Pfeffer1,2*

1Departments of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, USA

2The Center for Cancer Research, University of Tennessee Health Science Center, USA

3Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, USA

4Scientific Affairs, Amgen, Thousand oaks, CA, USA

5Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

6Department of Chemistry, College of Science, Fayoum University, Fayoum, Egypt

*Corresponding Author:
Lawrence M Pfeffer
Cancer Research Building
19 South Manassas Street (Room 154)
Memphis, TN 38163, USA
Tel: 901-448-7855
Fax: 901-448-3910; E-mail: [email protected]

Amira Hosni-Ahmed
Cancer Research Building
19 South Manassas Street (Room 319)
Memphis, TN 38163, USA
Tel: 901-825-8803
E-mail: [email protected]

Received date: August 07, 2014; Accepted date: September 22, 2014; Published date: September 25, 2014

Citation: Ahmed AH, Sims M, Jones TS, Patil R, Patil S, et al. (2014) EDL-360: A Potential Novel Antiglioma Agent. J Cancer Sci Ther 6:370-377. doi:10.4172/1948-5956.1000295

Copyright: © 2014 Ahmed AH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Glioma is a brain tumor that arises from glial cells or glial progenitor cells, and represents 80% of malignant brain tumor incidence in the United States. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor malignancy with fewer than 8% of patients with GBM surviving for more than 3 years. Over the past 10 years, despite improvement in diagnosis and therapies for cancer, the survival rate for high-grade glioma patients remains dismal. The main focus of our research is to identify potent novel antiglioma small molecules. We previously showed that EDL-360, a tetrahydroisoquinoline (THIQ) analog, as being highly cytotoxic to human glioma cell cultures. Here we show that EDL-360 significantly induced apoptosis in human glioma cell lines (U87 and LN18). However, in normal astrocytic cells, EDL-360 induced a modest G0/G1 cell cycle arrest but did not induce apoptosis. In an attempt to enhance EDL-360 induced cell death, we tested simultaneous treatment with EDL‑360 and embelin (an inhibitor of the anti-apoptotic protein, XIAP). We found that, glioma cells had significant lower viability when EDL‑360 and embelin were used in combination when compared to EDL-360 alone. We also used combination treatment of EDL-360 with decylubiquinone (dUb), a caspase-9 inhibitor, and found that the combination treatment induced a significant cell death when compared to treatment with EDL-360 alone. This is the first report that suggests that dUb has anticancer activity, and perhaps acts as a XIAP inhibitor. Finally, our in vivo data showed that EDL-360 treatment induced a partial regression in glioma tumorigenesis and induced cell death in the treated tumors as shown by H&E staining. Taken together these data suggests that EDL-360 has a potential therapeutic application for treating glioma, especially when combined with XIAP inhibitors.

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