Title :

Ascorbic acid (vitamin C) synergistically enhances the therapeutic effect of targeted therapy in chronic lymphocytic leukemia.

Author(s) :

Darwiche, Walaa [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Gomila, Cathy [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Ouled-Haddou, Hakim [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Naudot, Marie [Auteur]
CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 [CHIMERE]
Doualle, Cécile [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Morel, Pierre [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Nguyen-Khac, Florence [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Garçon, Loïc [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Marolleau, Jean-Pierre [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Ghamlouch, Hussein [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]

Journal title :

Journal of experimental & clinical cancer research

Abbreviated title :

J Exp Clin Cancer Res

Volume number :

39

Pages :

228

Publication date :

2020-11-11

ISSN :

1756-9966

English keyword(s) :

Chronic lymphocytic leukemia
Ascorbic acid
Vitamin C
Cytotoxicity
Drug combination

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Novel, less toxic, cost-effective and safe therapeutic strategies are needed to improve treatment of chronic lymphocytic leukemia (CLL). Ascorbic acid (AA, vitamin C) has shown a potential anti-cancer therapeutic ...
Show more >Background Novel, less toxic, cost-effective and safe therapeutic strategies are needed to improve treatment of chronic lymphocytic leukemia (CLL). Ascorbic acid (AA, vitamin C) has shown a potential anti-cancer therapeutic activity in several cancers. However, the anti-cancer effects of ascorbic acid on CLL B-cells have not been extensively studied. We aimed in this study to evaluate the in vitro therapeutic activity using clinically relevant conditions. Methods Primary CLL B-cells and two CLL cell lines were exposed to a dose that is clinically achievable by AA oral administration (250 μM), and cell death and potential mechanisms were assessed. The role of the protective CLL microenvironment was studied. Synergistic interaction between AA and CLL approved drugs (Ibrutinib, Idelalisib and Venetoclax) was also evaluated. Results Ascorbic acid is cytotoxic for CLL B-cells at low dose (250 μM) but spares healthy B-cells. Ascorbic-acid-induced cytotoxicity involved pro-oxidant damage through the generation of reactive oxygen species in the extracellular media and in CLL cells, and induced caspase-dependent apoptosis. We also found that AA treatment overcame the supportive survival effect provided by microenvironment including bone marrow mesenchymal stem cells, T-cell cues (CD40L + IL-4), cytokines and hypoxia. Our data suggest that resistance to AA could be mediated by the expression of the enzyme catalase in some CLL samples and by the glucose metabolite pyruvate. We also demonstrated that AA synergistically potentiates the cytotoxicity of targeted therapies used in or being developed for CLL. Conclusion These preclinical results point to AA as an adjuvant therapy with potential to further improve CLL treatments in combination with targeted therapies.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2023-11-15T07:54:18Z
2024-01-11T08:26:18Z