Chaetocin kills myeloma cells in vitro via induction of morphologic apoptosis accompanied by loss of mitochondrial membrane potential, PARP cleavage, and DNA ladder formation. (A) Transmission electron photomicrographs (4000×) of OCI-MY5 myeloma cells treated with DMSO or 100 nM chaetocin for 24 hours. (B) Effects of 24-hour exposure of OCI-MY5 myeloma cells to varying chaetocin concentrations on mitochondrial membrane depolarization (⊡) and apoptosis (•). Mitochondrial membrane potential was assessed via FACS, whereas apoptosis was assessed via fluorescence microscopy using Hoechst 33256 staining as described in “Patients, materials, and methods.” Results shown are representative of 4 independent experiments. (C) Induction of PARP cleavage in KAS 6/1 and OCI-MY5 myeloma cells by 100 nM chaetocin (time course). Upper bands represent the results of PARP immunoblotting, whereas the lower band indicates actin control immunoblotting. Results shown are representative of 4 independent experiments. (D) Electrophoresis of DNA extracted from diluent- or chaetocin-treated OCI-MY5 myeloma cells for 24 hours. Bands corresponding to uncleaved DNA and cleaved DNA ladders are indicated at the right. Results shown are representative of 3 independent experiments.