FIG. 1.

b-AP15 and bortezomib induce similar but not identical cellular responses. (A) The IC₅₀ values to b-AP15 (NSC687852) and bortezomib (NSC681239) of different cell lines in the NCI₆₀ cell line panel are plotted. Each dot represents the IC₅₀ values of the two drugs in one cell line. The result shows a weak, but statistically significant, correlation of the cytotoxic responses to the two drugs in the NCI₆₀ cell line panel. Statistical analysis: Pearson correlation coefficient. (B) Self-organizing map of the NCI₆₀ tumor cell line panel. Compounds segregate into six major response categories: mitosis (M); nucleic acid metabolism (S); metabolic stress and cell survival (Q); membrane function (N); kinases/phosphatases and oxidative stress (P); and four unexplored regions, R, F, J, and V (27). b-AP15 and bortezomib map to distinct regions of the Q-region. (C) mRNA abundance of 84 genes reported to respond to stress were quantified by real-time quantitative polymerase chain reaction. HCT116 cells were exposed to b-AP15 or bortezomib for 6 h, RNA was extracted, and mRNA levels were determined after reverse transcription. The yellow dotted line shows a y/x slope of 1; a y/x slope 1.67 was observed for transcript levels of cells exposed to b-AP15/bortezomib. (D) Expression of various classes of genes in HCT116 cells exposed to b-AP15 or bortezomib as fold induction (red dots=b-AP15; blue dots=bortezomib). (E, F) Expression of specific genes after exposure of HCT116 cells to b-AP15 or bortezomib (fold induction). Blue: HSF-1-regulated genes, green: genes associated with oxidative stress; red: genes associated with ER stress. IC₅₀, 50% inhibitory concentration; NCI, National Cancer Institute; HSF-1, heat shock factor protein 1.