Interaction of CCT020312 with paclitaxel.

<p><b>A) Paclitaxel-associated EIF2A phosphorylation in U-2OS and HCT116 cells.</b> U-2OS and HCT116 were exposed to 10 µM CCT020312 (CCT), DMSO or paclitaxel (taxol) for 4 hours. Cell lysates were analyzed by immunoblotting for P-S51-EIF2A and tubulin. <b>B) Proliferation inhibition by paclitaxel in the presence of CCT020312.</b> Cells were treated with increasing amounts (1–25 nM) of paclitaxel in the absence and presence of a fixed dose (2.5 µM) of CCT020312. Arrows denote proliferation inhibition in cells treated with 2.5 µM CCT020312 only. Cell lines were as indicated. <b>C) Multiple drugs effect analysis:</b> U-2OS and HCT116 cells were treated with escalating doses of paclitaxel, CCT020312 or their combination. Combination indices (CIs) for each dose are shown. The calculated mean CI and standard error is indicated. “CI excl” assumes agents act by a competing, mutually exclusive mechanism of action, “CI no-exl. assumes agents act through distinct, exclusive mechanisms of action <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028568#pone.0028568-Chou2" target="_blank">[57]</a>.