peloruside-a and Leukemia--Promyelocytic--Acute

Paclitaxel (Taxol®), a drug used to treat solid tumors of the breast, ovary and lung, stabilizes microtubules and arrests cells in G(2)/M of the cell cycle. Using two-dimensional differential in-gel electrophoresis (DIGE), we examined the proteomic response of a human HL-60 promyeloid leukemic cell line to paclitaxel. Our intention was to compare the effects of paclitaxel to those of a new-generation microtubule-stabilizing agent, peloruside A, investigated in an earlier study. In response to 100 nM paclitaxel treatment for 24 h, 21 identified proteins changed in abundance, with 13 increases and 8 decreases. In addition, 21 other unidentified proteins were also changed by treatment with paclitaxel. Using Western blotting, the transcription factor c-Myc was shown to be reduced in abundance by both drugs. Our results showed both differences and similarities at the single protein level between paclitaxel and peloruside A, although the same general classes of proteins: cytoskeletal, nucleic acid binding, stress, and apoptotic proteins, changed following exposure. The proteomic response to paclitaxel was more extensive than the response to an equipotent dose of peloruside A.

Topics: Antineoplastic Agents; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic; Down-Regulation; G2 Phase Cell Cycle Checkpoints; HL-60 Cells; Humans; Lactones; Leukemia, Promyelocytic, Acute; Neoplasm Proteins; Paclitaxel; Proteomics; Proto-Oncogene Proteins c-myc; Two-Dimensional Difference Gel Electrophoresis