Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs

Annamaria Cimini, Michele d'Angelo, Elisabetta Benedetti, Barbara D'Angelo, Giulio Laurenti, Andrea Antonosante, Loredana Cristiano, Antonella Di Mambro, Marcella Barbarino, Vanessa Castelli, Benedetta Cinque, Maria Grazia Cifone, Rodolfo Ippoliti, Francesca Pentimalli, Antonio Giordano

Research output: Contribution to journalArticle

Abstract

Glioblastoma, the most common brain tumor, is characterized by high proliferation rate, invasion, angiogenesis, and chemo- and radio-resistance. One of most remarkable feature of glioblastoma is the switch toward a glycolytic energetic metabolism that leads to high glucose uptake and consumption and a strong production of lactate. Activation of several oncogene pathways like Akt, c-myc, and ras induces glycolysis and angiogenesis and acts to assure glycolysis prosecution, tumor proliferation, and resistance to therapy. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes resulting in an overproduction of pyruvate and lactate. Metabolism of glioblastoma thus represents a key issue for cancer research. Flavopiridol is a synthetic flavonoid that inhibits a wide range of Cyclin-dependent kinase, that has been demonstrate to inactivate glycogen phosphorylase, decreasing glucose availability for glycolysis. In this work the study of glucose metabolism upon flavopiridol treatment in the two different glioblastoma cell lines. The results obtained point towards an effect of flavopiridol in glycolytic cells, thus suggesting a possible new use of this compound or flavopiridol-derived formulations in combination with anti-proliferative agents in glioblastoma patients.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusPublished - 2017

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Cimini, A., d'Angelo, M., Benedetti, E., D'Angelo, B., Laurenti, G., Antonosante, A., Cristiano, L., Di Mambro, A., Barbarino, M., Castelli, V., Cinque, B., Cifone, M. G., Ippoliti, R., Pentimalli, F., & Giordano, A. (2017). Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.25421