Journal
LEUKEMIA & LYMPHOMA
Volume 58, Issue 12, Pages 2905-2915Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2017.1317091
Keywords
Marine glycoside; frondoside A; AIF; caspase-independent apoptosis; Burkitt lymphoma
Categories
Funding
- Eppendorfer Krebs-und Leukamiehilfe e
- Department of Oncology, Hematology, Bone Marrow Transplantation
- Pneumology, Department of Medicine, University Hospital Hamburg-Eppendorf [20246, 20251]
- RFBR [1603-00553a]
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For patients with refractory or relapsed Burkitt lymphoma (BL), no standard therapy is available for second-line treatment to date. Nonfunctional caspases-dependent apoptosis pathways, inactivating p53 mutations and pro-survival autophagy prevent activity of conventional chemotherapy. Thus, new drugs bypassing these mechanisms of resistance are required. Here, we investigated the efficacy of the marine natural compound frondoside A (FrA) in eight BL cell lines. FrA revealed cytotoxic effects in all cell lines tested including the multiresistant CA46 cells. Remarkably, FrA induced caspases- and p53-independent apoptosis, which was characterized by decreased expression of antiapoptotic survivin and Bcl-2, mitochondria targeting (release of cytochrome C, HtrA2/Omi and the apoptosis-inducing factor (AIF), and altered production of ROS) and translocation of AIF to the nuclei. In addition, signs of inhibition of pro-survival autophagy were observed. Thus, FrA is a promising candidate for the treatment of refractory or relapsed BL revealing resistances to standard therapies.
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