Discovery of monocarbonyl curcumin-BTP hybrids as STAT3 inhibitors for drug-sensitive and drug-resistant breast cancer therapy.

ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) is a well-known antitumor target. Exogenous ROS insult can lead to selective cytotoxicity against cancer cells. A combination of STAT3 inhibition and "oxidation therapy" may be a new strategy to address the multidrug-resistance issue due to their important roles in the survival and drug resistance of cancer cells. Here, a series of novel curcumin-BTP hybrids were designed and evaluated as STAT3 inhibitors with ROS production activity. Compound 6b exerted the best antitumor activity and selectivity for MCF-7 and MCF-7/DOX cells (IC₅₀ = 0.52 μM and 0.40 μM, respectively), while its IC₅₀ value for MCF-10A breast epithelial cells was 7.72 μM. Furthermore, compound 6b suppressed STAT3 phosphorylation, nuclear trans

SUBMITTER: Zhang W 

PROVIDER: S-EPMC5387716 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature