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The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation
Abstract
C-1311 is a small molecule, which has shown promise in a number of preclinical 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.
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Authors (5)
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Shaliny Ramachandran Dr
- Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, The University of Oxford, Oxford, UK
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Grzegorz Dobrynin Dr
- Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, The University of Oxford, Oxford, UK
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Katarzyna B. Leszczynska Dr
- Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, The University of Oxford, Oxford, UK
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Ester M. Hammond Prof.
- Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, The University of Oxford, Oxford, UK
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Details
- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
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Oncotarget
no. 8,
pages 31187 - 31198,
ISSN: 1949-2553 - Language:
- English
- Publication year:
- 2017
- Bibliographic description:
- Skwarska A., Ramachandran S., Dobrynin G., Leszczynska K. B., Hammond E. M.: The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation// Oncotarget. -Vol. 8, iss. 19 (2017), s.31187-31198
- DOI:
- Digital Object Identifier (open in new tab) 10.18632/oncotarget.16102
- Verified by:
- Gdańsk University of Technology
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