Paclitaxel binding to human and murine MD-2.

ABSTRACT: Paclitaxel (PTX) is an important cancer chemotherapeutic agent that binds to beta-tubulin and prevents mitosis through microtubule overstabilization. Recent evidence also implicates PTX in the induction of apoptosis of cancer cells via the TLR4 innate immune pathway. The TLR4 accessory protein, MD-2, is an essential component for the species-specific proinflammatory activity of PTX on murine cells. However, whether PTX binds to human MD-2 and how MD-2 and TLR4 interact with PTX are not well defined. Recombinant human MD-2 (rhMD-2) was produced in a Pichia pastoris expression system, and the interaction between rhMD-2 and PTX was assessed by an enzyme-linked immunosorbent assay to show that PTX binds rhMD-2. Formation of the latter complex was found to be dose-dependent and inhibited by ant

SUBMITTER: Zimmer SM 

PROVIDER: S-EPMC2562052 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature