The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation
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 respons...
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| Format: | Journal article |
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Impact Journals
2017
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| _version_ | 1797098291116113920 |
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| author | Skwarska, A Ramachandran, S Dobrynin, G Leszczynska, K Hammond, E |
| author_facet | Skwarska, A Ramachandran, S Dobrynin, G Leszczynska, K Hammond, E |
| author_sort | Skwarska, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:07:22Z |
| format | Journal article |
| id | oxford-uuid:da626025-4e37-4a04-9659-132761bfce01 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:07:22Z |
| publishDate | 2017 |
| publisher | Impact Journals |
| record_format | dspace |
| spelling | oxford-uuid:da626025-4e37-4a04-9659-132761bfce012022-03-27T09:03:04ZThe imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:da626025-4e37-4a04-9659-132761bfce01Symplectic Elements at OxfordImpact Journals2017Skwarska, ARamachandran, SDobrynin, GLeszczynska, KHammond, EC-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. |
| spellingShingle | Skwarska, A Ramachandran, S Dobrynin, G Leszczynska, K Hammond, E The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title | The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title_full | The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title_fullStr | The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title_full_unstemmed | The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title_short | The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation |
| title_sort | imidazoacridinone c 1311 induces p53 dependent senescence or p53 independent apoptosis and sensitizes cancer cells to radiation |
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