Mithramycin A Enhances Tumor Sensitivity to Mitotic Catastrophe Resulting From DNA Damage.

ABSTRACT:

Purpose

Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response.

Methods and materials

Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology. Gene expression was evaluated using polymerase chain reaction arrays. In vivo tumor growth delay was used to evaluate the effects of MTA on radiosensitivity.

Results

Targeting of SP1 with small interfering RNA or MTA sensitized A549 and UM-UC-3 t

SUBMITTER: Scroggins BT 

PROVIDER: S-EPMC5777897 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature