A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy.

ABSTRACT: Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer "immuno-chemotherapy". Compound 2 effectively kills hormone-dependent, cisplatin-resistant human ovarian cancer cells, inhibiting IDO by transcriptional deregulation of the autocrine-signaling loop IDO-AHR-IL6, which blocks kynurenine production and promotes T-cell proliferation. Additionally, 1 and 2 display low t

SUBMITTER: Awuah SG 

PROVIDER: S-EPMC4772771 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature