Identification of a new class of natural product MDM2 inhibitor: In vitro and in vivo anti-breast cancer activities and target validation.

ABSTRACT: The MDM2 oncogene has been suggested as a molecular target for treating human cancers, including breast cancer. Most MDM2 inhibitors under development are targeting the MDM2-p53 binding, and have little or no effects on cancers without functional p53, such as advanced breast cancer. The present study was designed to develop a new class of MDM2 inhibitors that exhibit anticancer activity in MDM2-dependent and p53-independent manners. The selective MDM2 inhibitors were discovered by a computational structure-based screening, yielding a lead compound, termed JapA. We further found that JapA inhibited cell growth, decreased cell proliferation, and induced G2/M phase arrest and apoptosis in breast cancer cells through an MDM2-dependent mechanism, regardless of p53 status. It also inhibited the

SUBMITTER: Qin JJ 

PROVIDER: S-EPMC4413606 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature