EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo

Xiang Di Wang, Natalie E. Freeman, Renukadevi Patil, Shivaputra A. Patil, Suchareeta Mitra, William E. Orr, Clint W. Abner, Charles Yates, Duane Miller, Eldon E. Geisert

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

To investigate the effectiveness of EDL-291, a 6,7-dimethoxy-1-[4-(4- methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline dihydrochloride compound, in inhibiting the survival of glioblastoma in vitro and in vivo. Dose-response curves were generated to determine the EC50 in rat and human glioblastoma cell lines by treatment with different dilutions of EDL-291. To evaluate the architecture of the glioblastoma cells after treatment with EDL-291, the rat and human glioblastoma cells were stained with Mito Tracker Green FM. To determine whether autophagy was induced in EDL-291-treated glioblastoma cells, both rat and human glioblastoma cell lines were stained with acridine orange and light chain-3 immunoblots were performed. The efficacy of EDL-291 was monitored in vivo using a rat glioblastoma model. Rat glioblastoma cells were transplanted into an intracranial rat model, followed by infusions of saline, a low dose of EDL-291 (20 mg/kg for the first half hour, followed by 40 mg/kg EDL-291 in saline for 4 h), or a high dose of EDL-291 (60 mg/kg for the first half hour, followed by 90 mg/kg EDL-291 for 4 h). EDL-291 inhibits glioblastoma in vitro by destroying the mitochondria as shown with Mito Tracker Green FM. Acridine orange staining and light chain-3 immunoblots suggest that autophagy is induced when glioblastoma cells are treated with EDL-291. In vivo, a low dosage of EDL-291 is sufficient and effective in reducing glioblastoma tumor size. EDL-291 selectively induces cell death in rat and human glioblastoma cell lines by the induction of autophagy. EDL-291 exhibits antiglioblastoma effects both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)494-504
Number of pages11
JournalAnti-Cancer Drugs
Volume23
Issue number5
DOIs
StatePublished - Jun 1 2012

Fingerprint

Glioblastoma
Autophagy
Acridine Orange
EDL-291
isoquinoline
In Vitro Techniques
Cell Line
Light
Mitochondria
Cell Death
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research
  • Oncology

Cite this

Wang, X. D., Freeman, N. E., Patil, R., Patil, S. A., Mitra, S., Orr, W. E., ... Geisert, E. E. (2012). EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo. Anti-Cancer Drugs, 23(5), 494-504. https://doi.org/10.1097/CAD.0b013e328351ee4f

EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo. / Wang, Xiang Di; Freeman, Natalie E.; Patil, Renukadevi; Patil, Shivaputra A.; Mitra, Suchareeta; Orr, William E.; Abner, Clint W.; Yates, Charles; Miller, Duane; Geisert, Eldon E.

In: Anti-Cancer Drugs, Vol. 23, No. 5, 01.06.2012, p. 494-504.

Research output: Contribution to journalArticle

Wang, XD, Freeman, NE, Patil, R, Patil, SA, Mitra, S, Orr, WE, Abner, CW, Yates, C, Miller, D & Geisert, EE 2012, 'EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo', Anti-Cancer Drugs, vol. 23, no. 5, pp. 494-504. https://doi.org/10.1097/CAD.0b013e328351ee4f
Wang, Xiang Di ; Freeman, Natalie E. ; Patil, Renukadevi ; Patil, Shivaputra A. ; Mitra, Suchareeta ; Orr, William E. ; Abner, Clint W. ; Yates, Charles ; Miller, Duane ; Geisert, Eldon E. / EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo. In: Anti-Cancer Drugs. 2012 ; Vol. 23, No. 5. pp. 494-504.
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