Mutations in the proteolipid subunits of the vacuolar H+-ATPase provide resistance to indolotryptoline natural products.

ABSTRACT: Indolotryptoline natural products represent a small family of structurally unique chromopyrrolic acid-derived antiproliferative agents. Like many prospective anticancer agents before them, the exploration of their potential clinical utility has been hindered by the limited information known about their mechanism of action. To study the mode of action of two closely related indolotryptolines (BE-54017, cladoniamide A), we selected for drug resistant mutants using a multidrug resistance-suppressed (MDR-sup) Schizosaccharomyces pombe strain. As fission yeast maintains many of the basic cancer-relevant cellular processes present in human cells, it represents an appealing model to use in determining the potential molecular target of antiproliferative natural products through resistant mutant sc

SUBMITTER: Chang FY 

PROVIDER: S-EPMC4238801 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature