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Hosni-Ahmed A, Sims M, Jones TS, et al. EDL-360: A Potential Novel Antiglioma Agent. J Cancer Sci Ther. 2014;6(9):370-377doi: 10.4172/1948-5956.1000295.
Hosni-Ahmed, A., Sims, M., Jones, T. S., Patil, R., Patil, S., Abdelsamed, H., Yates, C. R., Miller, D. D., & Pfeffer, L. M. (2014). EDL-360: A Potential Novel Antiglioma Agent. Journal of cancer science & therapy, 6(9), 370-377. https://doi.org/10.4172/1948-5956.1000295
Hosni-Ahmed, Amira, et al. "EDL-360: A Potential Novel Antiglioma Agent." Journal of cancer science & therapy vol. 6,9 (2014): 370-377. doi: https://doi.org/10.4172/1948-5956.1000295
Hosni-Ahmed A, Sims M, Jones TS, Patil R, Patil S, Abdelsamed H, Yates CR, Miller DD, Pfeffer LM. EDL-360: A Potential Novel Antiglioma Agent. J Cancer Sci Ther. 2014 Sep 25;6(9):370-377. doi: 10.4172/1948-5956.1000295. PMID: 25574358; PMCID: PMC4285352.
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J Cancer Sci Ther. 2014 Sep 25;6(9):370-377. doi: 10.4172/1948-5956.1000295.

EDL-360: A Potential Novel Antiglioma Agent.

Journal of cancer science & therapy

Amira Hosni-Ahmed, Michelle Sims, Terreia S Jones, Renukadevi Patil, Shivaputra Patil, Hossam Abdelsamed, Charles R Yates, Duane D Miller, Lawrence M Pfeffer

Affiliations

  1. Departments of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, USA ; The Center for Cancer Research, University of Tennessee Health Science Center, USA ; Department of Chemistry, College of Science, Fayoum University, Fayoum, Egypt.
  2. Departments of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, USA ; The Center for Cancer Research, University of Tennessee Health Science Center, USA.
  3. Scientific Affairs, Amgen, Thousand oaks, CA, USA.
  4. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, USA.
  5. Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA ; Department of Chemistry, College of Science, Fayoum University, Fayoum, Egypt.

PMID: 25574358 PMCID: PMC4285352 DOI: 10.4172/1948-5956.1000295

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

Keywords: Angiogenesis; Ovarian cancer; PARP inhibitors

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