The combination of Bleomycin with TRAIL agonists or PKC inhibitors sensitizes solid tumor cells to BLM-mediated apoptosis: new strategies to overcome chemotherapy resistance of tumors

Autor: Sonia Aroui, Ali Bettaieb, Abderraouf Kenani, Souhir Brahim, Jean F. Jeannin, Rahamata Ali
Přispěvatelé: Faculté de Médecine de Monastir [Tunisie], Laboratoire d'Immunologie et Immunothérapie des Cancers ( LIIC ), École pratique des hautes études ( EPHE ) -Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Bourgogne (UB), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Medicinal Chemistry Research
Medicinal Chemistry Research, Springer Verlag, 2017, pp.1-7. 〈https://link.springer.com/article/10.1007/s00044-017-1915-9〉. 〈10.1007/s00044-017-1915-9〉
Medicinal Chemistry Research, Springer Verlag, 2017, pp.1-7. ⟨10.1007/s00044-017-1915-9⟩
ISSN: 1054-2523
1554-8120
DOI: 10.1007/s00044-017-1915-9〉.
Popis: IF 1.436; International audience; In this study we evaluated the effects of low dose of bleomycin in an associative treatment strategy in solid tumor cells. For this purpose, Human and murine colon cancer (SW480, HCT8, and CT26), and murine melanoma (B16-F10) cells were treated with different agents including protein kinase C, and c-jun NH2-terminal kinase inhibitors, and tumor necrosis factor-related apoptosis-inducing ligand. Apoptosis was identified by morphological criteria. Reactive oxygen species are evaluated by flow cytometry. Our data showed that bleomycin (100 µM) induced apoptosis in all the four cell lines tested with a level ranging from 30 to 60%. However, at lower dose (25 µM), bleomycin was less efficient to trigger apoptosis. In contrast, when bleomycin (25 µM) was combined with the protein kinase C inhibitor chelerythrine, or tumor necrosis factor-related apoptosis-inducing ligand, it elicited more apoptotic cell death ranging from 40 to 75%, depending on the cell type, whereas when it was associated with the c-jun NH2-terminal kinase inhibitor SP600125, bleomycin displayed different cell death responses. If bleomycin and SP600125 enhanced apoptosis in two colon cancer cells, HCT-8, and CT26, they reduced to 50% apoptosis in the melanoma B16-F10 cells, and were not synergistic in the human colon cancer cells, SW480. This synergism seemed to rely partially to reactive oxygen species, because N-acetyl cysteine inhibited apoptosis in some cells and with some agents. These findings indicate that tumor necrosis factor-related apoptosis-inducing ligand, and protein kinase C inhibition can represent candidates for improved cancer chemotherapy.
Databáze: OpenAIRE