Epothilon B

Epothilone B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC₅₀ values in the low nanomolar range. Colony forming assays showed a synergistic radiosensitive effect on both cell lines which was dependent on incubation time and applied concentration of epothilone B. The γH2AX assays demonstrated that ionizing radiation combined with the drug resulted in a concentration-dependent increase in the number of double-strand breaks and suggested a reduction in DNA repair capacity. Epothilone B produced enhanced microtubule bundling and abnormal spindle formation as revealed by immunofluo-rescence microscopy and caused microtubule formation from purified tubulin.

Therefore, various pH-responsive drug delivery systems have been designed to release enclosed drugs at the target site before lysosomal degradation occurs. Recently, we have shown that rHDL can be composed to release paclitaxel (PTX) in a pH-responsive manner. Perhaps because endosomal escape of the PTX was facilitated, the pH-responsive PTX-rHDL was more potent than normal PTX-rHDL. Inspired by this success, we determined to assemble the pH-responsive rHDL of epothilone B (EpoB), which is extremely more potent than PTX. epothilone B (EpoB) is a member of the epothilone class, which is a group of microtubule-stabilizing agents. epothilone B (EpoB) binds to β-tubulin subunits of microtubules with higher affinity than other taxanes. Most cancer cells overexpressing human epidermal growth factor receptor 2 (HER2) are resistant to taxane chemotherapy.