Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters.

ABSTRACT: Many cancer therapeutic agents elicit resistance that renders them ineffective and often produces cross-resistance to other drugs. One of the most common mechanisms of resistance involves P-glycoprotein (Pgp)-mediated drug efflux. To address this problem, new agents have been sought that are less prone to inducing resistance and less likely to serve as substrates for Pgp efflux. An alternative to this approach is to deliver established agents as molecular transporter conjugates into cells through a mechanism that circumvents Pgp-mediated efflux and allows for release of free drug only after cell entry. Here we report that the widely used chemotherapeutic agent Taxol, ineffective against Taxol-resistant human ovarian cancer cell lines, can be incorporated into a releasable octaarginine conj

SUBMITTER: Dubikovskaya EA 

PROVIDER: S-EPMC2527877 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature