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Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs
Author(s) -
Cimini Annamaria,
d'Angelo Michele,
Benedetti Elisabetta,
D'Angelo Barbara,
Laurenti Giulio,
Antonosante Andrea,
Cristiano Loredana,
Di Mambro Antonella,
Barbarino Marcella,
Castelli Vanessa,
Cinque Benedetta,
Cifone Maria Grazia,
Ippoliti Rodolfo,
Pentimalli Francesca,
Giordano Antonio
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25421
Subject(s) - glycolysis , angiogenesis , cancer research , anaerobic glycolysis , flux (metallurgy) , protein kinase b , pi3k/akt/mtor pathway , warburg effect , biology , kinase , biochemistry , glycogen phosphorylase , chemistry , microbiology and biotechnology , metabolism , glycogen , signal transduction , organic chemistry
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. J. Cell. Physiol. 232: 312–322, 2017. © 2016 Wiley Periodicals, Inc.