Flavopiridol inhibits the growth of GL261 gliomas in vivo: Implications for malignant glioma therapy

Elizabeth W. Newcomb, Cristina Tamasdan, Yolanda Entzminger, Elizabeth Arena, Tona Schnee, Mimi Kim, Diana Crisan, Yevgeniy Lukyanov, Douglas C. Miller, David Zagzag

Research output: Contribution to journalArticle

Abstract

The mechanism of action of many chemotherapeutic agents targets the cell cycle. Recently, we demonstrated cytotoxic and other anti-tumor effects of flavopiridol, the first synthetic cyclin dependent kinase (CDK) inhibitor to enter clinical trials, on the murine GL261 glioma cell line in vitro (Newcomb et al., Cell Cycle 2003; 2:243). Given that flavopiridol has demonstrated anti-tumor activity in several human xenograft models, we wanted to evaluate it for anti-glioma activity in vivo in our established subcutaneous and intracranial GL261 experimental tumor models. In particular, the intracranial animal model recapitulates many of the histopathological and biological features of human high-grade glioma including both necrosis with pseudopalisading and invasion of the brain adjacent to tumor. Here we tested the activity of flavopiridol against tumors formed by GL261 cells, first as subcutaneous implants, and then in the intracranial model. We demonstrate efficacy of flavopiridol as a single modality treatment in delaying tumor growth in both animal models. We hypothesize that flavopiridol treatment induced tumor growth delay by two possible mechanisms involving growth arrest combined with recruitment of tumor cells to S-phase. Based on our findings, flavopiridol should be considered as a treatment approach for patients with high-grade glioma.

Original languageEnglish (US)
Pages (from-to)218-222
Number of pages5
JournalCell Cycle
Volume3
Issue number2
StatePublished - Feb 2004

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alvocidib
Glioma
Growth
Neoplasms
Therapeutics
Cell Cycle
Animal Models
Cyclin-Dependent Kinases
S Phase
Heterografts

Keywords

  • Flavopiridol
  • GL261 Glioma Model
  • S-phase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Newcomb, E. W., Tamasdan, C., Entzminger, Y., Arena, E., Schnee, T., Kim, M., ... Zagzag, D. (2004). Flavopiridol inhibits the growth of GL261 gliomas in vivo: Implications for malignant glioma therapy. Cell Cycle, 3(2), 218-222.

Flavopiridol inhibits the growth of GL261 gliomas in vivo : Implications for malignant glioma therapy. / Newcomb, Elizabeth W.; Tamasdan, Cristina; Entzminger, Yolanda; Arena, Elizabeth; Schnee, Tona; Kim, Mimi; Crisan, Diana; Lukyanov, Yevgeniy; Miller, Douglas C.; Zagzag, David.

In: Cell Cycle, Vol. 3, No. 2, 02.2004, p. 218-222.

Research output: Contribution to journalArticle

Newcomb, EW, Tamasdan, C, Entzminger, Y, Arena, E, Schnee, T, Kim, M, Crisan, D, Lukyanov, Y, Miller, DC & Zagzag, D 2004, 'Flavopiridol inhibits the growth of GL261 gliomas in vivo: Implications for malignant glioma therapy', Cell Cycle, vol. 3, no. 2, pp. 218-222.
Newcomb EW, Tamasdan C, Entzminger Y, Arena E, Schnee T, Kim M et al. Flavopiridol inhibits the growth of GL261 gliomas in vivo: Implications for malignant glioma therapy. Cell Cycle. 2004 Feb;3(2):218-222.
Newcomb, Elizabeth W. ; Tamasdan, Cristina ; Entzminger, Yolanda ; Arena, Elizabeth ; Schnee, Tona ; Kim, Mimi ; Crisan, Diana ; Lukyanov, Yevgeniy ; Miller, Douglas C. ; Zagzag, David. / Flavopiridol inhibits the growth of GL261 gliomas in vivo : Implications for malignant glioma therapy. In: Cell Cycle. 2004 ; Vol. 3, No. 2. pp. 218-222.
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