Novel tubulin polymerization inhibitors overcome multidrug resistance and reduce melanoma lung metastasis.

ABSTRACT:

Purpose

To evaluate abilities of 2-aryl-4-benzoyl-imidazoles (ABI) to overcome multidrug resistance (MDR), define their cellular target, and assess in vivo antimelanoma efficacy.

Methods

MDR cell lines that overexpressed P-glycoprotein, MDR-associated proteins, and breast cancer resistance protein were used to evaluate ABI ability to overcome MDR. Cell cycle analysis, molecular modeling, and microtubule imaging were used to define ABI cellular target. SHO mice bearing A375 human melanoma xenograft were used to evaluate ABI in vivo antitumor activity. B16-F10/C57BL mouse melanoma lung metastasis model was used to test ABI efficacy to inhibit tumor lung metastasis.

Results

ABIs showed similar potency to MDR cells compared to matching parent cells. ABIs were identified t

SUBMITTER: Wang Z 

PROVIDER: S-EPMC3659804 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature