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.

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@article{bf5cb8e8bcb44e56942d8bb83335d62c,
title = "Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells",
abstract = "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.",
keywords = "Journal Article",
author = "Dyshlovoy, {Sergey A} and Stefanie Rast and Jessica Hauschild and Katharina Otte and Alsdorf, {Winfried H} and Ramin Madanchi and Kalinin, {Vladimir I} and Silchenko, {Alexandra S} and Avilov, {Sergey A} and Judith Dierlamm and Friedemann Honecker and Stonik, {Valentin A} and Carsten Bokemeyer and {von Amsberg}, Gunhild",
year = "2017",
month = dec,
doi = "10.1080/10428194.2017.1317091",
language = "English",
volume = "58",
pages = "2905--2915",
journal = "LEUKEMIA LYMPHOMA",
issn = "1042-8194",
publisher = "informa healthcare",
number = "12",

}

RIS

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 articles

C2 - 28508718

VL - 58

SP - 2905

EP - 2915

JO - LEUKEMIA LYMPHOMA

JF - LEUKEMIA LYMPHOMA

SN - 1042-8194

IS - 12

ER -