Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263

Autor: Camille Huart, Maude Fransolet, Catherine Demazy, Benjamin Le Calvé, Stéphane Lucas, Carine Michiels, Anne-Catherine Wéra
Přispěvatelé: UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancers; Volume 14; Issue 6; Pages: 1460
Huart, C, Fransolet, M, Demazy, C, Le Calvé, B, Lucas, S, Michiels, C & Wéra, A C 2022, ' Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263 ', Cancers, vol. 14, no. 6, 1460 . https://doi.org/10.3390/cancers14061460
Cancers, Vol. 14, no.6, p. 1460 (2022)
ISSN: 2072-6694
DOI: 10.3390/cancers14061460
Popis: Radiotherapy (RT) is a key component of cancer treatment. Although improvements have been made over the years, radioresistance remains a challenge. For this reason, a better understanding of cell fates in response to RT could improve therapeutic options to enhance cell death and reduce adverse effects. Here, we showed that combining RT (photons and protons) to noncytotoxic concentration of PARP inhibitor, Olaparib, induced a cell line-dependent senescence-like phenotype. The senescent cells were characterized by morphological changes, an increase in p21 mRNA expression as well as an increase in senescence-associated β-galactosidase activity. We demonstrated that these senescent cells could be specifically targeted by Navitoclax (ABT-263), a Bcl-2 family inhibitor. This senolytic drug led to significant cell death when combined with RT and Olaparib, while limited cytotoxicity was observed when used alone. These results demonstrate that a combination of RT with PARP inhibition and senolytics could be a promising therapeutic approach for cancer patients.
Databáze: OpenAIRE
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