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Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells

2017; Taylor & Francis; Volume: 58; Issue: 12 Linguagem: Inglês

10.1080/10428194.2017.1317091

1042-8194

Sergey A. Dyshlovoy, Stefanie Rast, Jessica Hauschild, Katharina Otte, Winfried Alsdorf, Ramin Madanchi, Vladimir I. Kalinin, Alexandra S. Silchenko, Sergey A. Avilov, Judith Dierlamm, Friedemann Honecker, Valentin A. Stonik, Carsten Bokemeyer, Gunhild von Amsberg,

Seaweed-derived Bioactive Compounds

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.