Lonidamine and arsenic trioxide bypass the resistance of TPA-differentiated HL60 cells to etoposide.

Undifferentiated (▴, HL60), TPA-differentiated (●, HL-TPA), and Bcl-2 overexpressing (▪, HL-BCL2) HL60 cells were treated with 50 μM etoposide (VP16), 200 μM lonidamine (LND), or 4 μM arsenic trioxide (As₂O₃) for indicated times. (A) Apoptotic DNA fragmentation was quantified with the use of a filter elution assay. Values from 1 of 2 independent experiments are shown (mean ± SD of triplicate samples). (B) Western blot analysis of PARP cleavage in whole-cell extracts from HL60, HL-TPA, and HL-BCL2 cells, either untreated (−) or treated (+) with 50 μM VP16 for 6 hours, 200 μM LND for 48 hours, or 4 μM As₂O₃ for 48 hours. Numbers are molecular weights in kilodaltons. *Cleavage product. Loading was checked with the use of an antihuman HSC70 mAb.