Antitumoral Activity of Flavone L-86-8275

Flavopiridol Inhibits Glycogen Phosphorylase by Binding at the Inhibitor Site

“…The IC 50 value for glucose was calculated to be 19.7 Ϯ 1.3 mM. Kaiser et al 2 found an IC 50 ϭ 1 M for flavopiridol inhibition of rabbit muscle GPb, when tested in the direction of glycogen breakdown, in the presence of 0.8 mM AMP, 20 mM phosphate, pH 7.2, 0.1% glycogen, and 25°C. This difference may well be a consequence of the reaction being measured in the opposite direction of catalysis and the different substrate concentrations used.…”

“…Flavopiridol (L86 -8275, Scheme I), a flavonoid, has been shown to be a potent, competitive inhibitor (with respect to ATP) of cyclin-dependent kinases (CDKs) 1 with IC 50 values between 0.2 and 0.4 M (1) and to have antiproliferative and cytotoxic activity on certain tumor cell lines in vitro and in vivo (2)(3)(4)(5). The compound is currently in phase II trials, the first CDK inhibitor to be tested in clinical trials (5,6).…”

“…2 Furthermore, flavopiridol treatment of A549 non-small cell lung carcinoma cells resulted in an increase in glycogen accumulation. These findings raise the possibility that this antitumor drug may also interfere with glucose homeostasis in addition to the effects on the cell cycle through CDK inhibition.…”

Importance pharmacologique des dérivés polyphénoliques

“…3 ). Ce dernier compose a presente des effets antitumoraux significatifs in vitro et in vivo prometteurs en vue d'etudes cliniques ulterieures (Sedlacek eta/., 1991, Czech et al, 1995.…”

Effect of P-glycoprotein on flavopiridol sensitivity

“…This agent inhibits proliferation (Kaur et al, 1992;Czech et al, 1995;Carlson et al, 1996;Sedlacek et al, 1996;Drees et al, 1997) and induces apoptosis in a variety of human cancer cells and cell lines (Bible and Kaufmann, 1996;de Azevedo et al, 1996;König et al, 1997;Schwartz et al, 1997;Arguello et al, 1998;Brüsselbach et al, 1998;Byrd et al, 1998;Parker et al, 1998;Patel et al, 1998). Based on its unique mechanism of action (Losiewicz et al, 1994), its ability to kill noncycling tumour cells (Bible and Kaufmann, 1996;Byrd et al, 1998) and its promising antitumour activity in xenograft models (Czech et al, 1995;Drees et al, 1997;Arguello et al, 1998;Patel et al, 1998), flavopiridol has entered phase I and phase II (Wright et al, 1998) testing as a single agent as well as phase I trials in combination with paclitaxel or cisplatin (Wright et al, 1998).…”