Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells
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Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells. / Dyshlovoy, Sergey A; Rast, Stefanie; Hauschild, Jessica; Otte, Katharina; Alsdorf, Winfried H; Madanchi, Ramin; Kalinin, Vladimir I; Silchenko, Alexandra S; Avilov, Sergey A; Dierlamm, Judith; Honecker, Friedemann; Stonik, Valentin A; Bokemeyer, Carsten; von Amsberg, Gunhild.
In: LEUKEMIA LYMPHOMA, Vol. 58, No. 12, 12.2017, p. 2905-2915.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells
AU - Dyshlovoy, Sergey A
AU - Rast, Stefanie
AU - Hauschild, Jessica
AU - Otte, Katharina
AU - Alsdorf, Winfried H
AU - Madanchi, Ramin
AU - Kalinin, Vladimir I
AU - Silchenko, Alexandra S
AU - Avilov, Sergey A
AU - Dierlamm, Judith
AU - Honecker, Friedemann
AU - Stonik, Valentin A
AU - Bokemeyer, Carsten
AU - von Amsberg, Gunhild
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1080/10428194.2017.1317091
DO - 10.1080/10428194.2017.1317091
M3 - SCORING: Journal article
C2 - 28508718
VL - 58
SP - 2905
EP - 2915
JO - LEUKEMIA LYMPHOMA
JF - LEUKEMIA LYMPHOMA
SN - 1042-8194
IS - 12
ER -
