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Potentiating Effect of the Flavonolignan (‐)‐Hydnocarpin in Combination with Vincristine in a Sensitive and P‐gp‐Expressing Acute Lymphoblastic Leukemia Cell Line
Author(s) -
Bueno Pérez Lynette,
Pan Li,
Sass Ellen,
Gupta Sneha V.,
Lehman Amy,
Kinghorn A. Douglas,
Lucas David M.
Publication year - 2013
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4903
Subject(s) - vincristine , growth inhibition , cell culture , cell growth , medicine , leukemia , pharmacology , cancer research , lymphoblastic leukemia , biology , immunology , chemotherapy , biochemistry , cyclophosphamide , genetics
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.