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 5 μM, vincristine‐mediated growth inhibition in the 697‐R cells increased significantly over the sum of the individual agents to 72% ( p  ≤ 0.0001) 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 10 μM (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 © 2012 John Wiley & Sons, Ltd.