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C-1311 is a small molecule, which has shown promise in a number of pre-clinical and clinical studies. However, the biological response to C-1311 exposure is complicated and has been reported to involve a number of cell fates. Here, we investigated the molecular signaling which determines the response to C-1311 in both cancer and non-cancer cell lines. For the first time we demonstrate that the tumor suppressor, p53 plays a key role in cell fate determination after C-1311 treatment. In the presence of wild-type p53, cells exposed to C-1311 entered senescence. In contrast, cells lines without functional p53 underwent mitotic catastrophe and apoptosis. C-1311 also induced autophagy in a non-p53-dependent manner. Cells in hypoxic conditions also responded to C-1311 in a p53-dependent manner, suggesting that our observations are physiologically relevant. Most importantly, we show that C-1311 can be effectively combined with radiation to improve the radiosensitivity of a panel of cancer cell lines. Together, our data suggest that C-1311 warrants further clinical testing in combination with radiotherapy for the treatment of solid tumors.

Original publication

DOI

10.18632/oncotarget.16102

Type

Journal article

Journal

Oncotarget

Publication Date

09/05/2017

Volume

8

Pages

31187 - 31198

Keywords

C-1311/Symadex, apoptosis, p53, radiation, senescence, Aminoacridines, Antineoplastic Agents, Apoptosis, Cell Cycle, Cell Line, Tumor, Cellular Senescence, Dose-Response Relationship, Radiation, Gene Knockout Techniques, Humans, Mitosis, Radiation Tolerance, Radiation-Sensitizing Agents, Tumor Suppressor Protein p53