Potentiating Effect of the Flavonolignan (-)-Hydnocarpin in Combination with Vincristine in a Sensitive and P-gp-Expressing Acute Lymphoblastic Leukemia Cell Line

The potentiating action of the flavonolignan, (-)-hydnocarpin, in combination with vincristine was evaluated in the 697 acute lymphoblastic leukemia cell line and a P-gp-expressing variant, 697-R. Vincristine at 3 nM caused nearly complete growth inhibition in 697 cells versus a 17% growth inhibition in 697-R cells. When combined with (-)-hydnocarpin at concentrations of 10 and 5M, vincristine-mediated growth inhibition in the 697-R cells increased significantly over the sum of the individual agents to 72% (p0.0001) and 41% (p=0.0256), respectively. Vincristine at 1.5 nM (66% growth inhibition) and 0.75 nM (39% growth inhibition) combined with (-)-hydnocarpin at 10M (42% growth inhibition) in the 697 cells caused a significant increase in growth inhibition to 83% (p=0.03) and to 61% (p<0.0001), respectively, when compared to vincristine treatment as a single agent. To investigate the mechanism for the vincristine re-sensitization caused by (-)-hydnocarpin, the P-gp inhibitory effect of (-)-hydnocarpin was evaluated. Copyright (c) 2012 John Wiley & Sons, Ltd.