title: DNA intercalator korkormicin A preferentially kills tumor cells expressing wild type p53.
abstract: Korkormicin A belongs to a family of nature-produced cyclic depsipeptides. It has potent antitumor activity against both leukemia cell P388 and carcinoma cell M109. To further explore its potential as a cancer therapeutic, the mechanism of its antitumor activity was investigated. We found that korkormicin A can bind to DNA through intercalation. It also induces p53 phosphorylation, which leads to inhibition of p53 degradation and activation of p53-dependent transcription. Furthermore, korkormicin A preferentially induces apoptosis in transformed cells retaining wild type p53. As it has been shown that p53 usually induces apoptosis in transformed cells, but only growth arrest in untransformed cells, these results indicate that korkormicin A is a potential antitumor agent for cancers with wild type p53.
authors.affiliation: Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Jirouta
authors.initials: J
authors.lastname: Kitagaki
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D047630:Depsipeptides / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D007364:Intercalating Agents; D016159:Tumor Suppressor Protein p53; C568480:korkormicin A; D004247:DNA