Effects, in an in-vivo model system, of 1,2,3,4-tetrahydroisoquinoline on glioma.

Abstract

The effects of 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol (EDL-155) on the growth of glioma was tested in vitro and in vivo. Normal cultured rat astrocytes and C6 rat glioma were used as a differential screen to test the effects of EDL-155. The compound was preferentially cytotoxic for C6 glioma (EC50=1.5 micromol/l) relative to cultured neonatal astrocytes (EC50=27.4 micromol/l). When compared with a standard chemotherapeutic agent, carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea), or temozolomide, EDL-155 was more selective and more potent in our differential tissue culture assay. The effect of EDL-155 was also tested in an animal model in which C6 glioma was transplanted into the brains of Sprague-Dawley rats. EDL-155 was delivered directly onto the tumor by an osmotic minipump directly into the brain or by intraperitoneal injection. Animals treated with EDL-155 had significantly smaller tumors than did control animals treated with carrier solution. We observed anatomical changes in cultured glioma cells treated with EDL-155 that were consistent with selective destruction of mitochondria and the induction of autophagy. These changes were not observed in normal astrocytes cultured from rat pups. The selective killing of glioma in tissue culture and in the rat brain models indicates that EDL-155 has potential therapeutic value in treating this type of brain cancer.

• Authors: Gyong-Suk Kang, Xiang Di Wang, Michael L Mohler, Oleg V Kirichenko, Renukadevi Patil, William E Orr, Duane D Miller, Eldon E Geisert
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 19 Issue 9 Pg. 859-70 (Oct 2008) ISSN: 0959-4973 [Print] England
• PMID: 18766000 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• EDL-155
• Tetrahydroisoquinolines
• Dacarbazine
• Carmustine
• Temozolomide

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Astrocytes (drug effects)
• Brain Neoplasms (drug therapy)
• Carmustine (therapeutic use)
• Cell Line, Tumor
• Dacarbazine (analogs & derivatives, therapeutic use)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Glioma (drug therapy)
• Male
• Rats
• Rats, Sprague-Dawley
• Temozolomide
• Tetrahydroisoquinolines (therapeutic use)
• Tissue Culture Techniques
• Xenograft Model Antitumor Assays