Synergistic Bcl-2 inhibition by ABT-737 and cyclosporine A

被引:10
作者
Cippa, Pietro E. [1 ,2 ]
Kamarashev, Jivko [3 ]
Chen, Jin [1 ,2 ]
Kraus, Anna K. [1 ,2 ]
Segerer, Stephan [2 ,4 ]
Feldmeyer, Laurence [3 ]
Fehr, Thomas [1 ,2 ]
机构
[1] Univ Zurich, Inst Physiol, Zurich, Switzerland
[2] Univ Zurich Hosp, Div Nephrol, CH-8091 Zurich, Switzerland
[3] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland
[4] Univ Zurich, Dept Anat, Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
Bcl-2; ABT-737; Calcineurin; Cyclosporine A; Lymphocyte; Melanocyte; FAMILY ANTAGONIST ABT-737; T-LYMPHOCYTES; BCL-2-DEFICIENT MICE; CELL-DEATH; APOPTOSIS; CALCINEURIN; HOMEOSTASIS; MECHANISMS; RESISTANCE; PROTEINS;
D O I
10.1007/s10495-012-0778-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Survival of lymphocytes and melanocyte stem cells critically depends on B cell lymphoma 2 (Bcl-2). In T lymphocytes, a basal calcineurin activity maintains Bcl-2 expression in na < ve cells, and the activation of the calcineurin pathway orchestrates the regulation of the intrinsic apoptosis pathway after antigen recognition. Therefore, calcineurin inhibitors might potentiate the pro-apoptotic effect of pharmacological Bcl-2 inhibitors on lymphatic cells. In vitro, a reduced Bcl-2 expression in lymphocytes exposed to calcineurin inhibitors increased their sensitivity to the small molecule Bcl-2 inhibitor ABT-737. This correlated with an augmented pro-apoptotic activity of ABT-737 on lymphocytes in combination with cyclosporine A in na < ve mice in vivo. Interestingly, similar processes were observed in melanocytes. ABT-737 induced a fur depigmentation at the site of injection, and this effect was expanded to a generalized depigmentation in combination with cyclosporine A. Thus, inhibiting calcineurin increases the pro-apoptotic potency of ABT-737 in cells depending on Bcl-2 for survival. The increased efficacy of Bcl-2 inhibitors in combination with cyclosporine A might be relevant to exploit their anti-neoplastic and immuno-modulatory properties.
引用
收藏
页码:315 / 323
页数:9
相关论文
共 50 条
[41]   Synergistic killing of colorectal cancer cells by oxaliplatin and ABT-737 [J].
Raats, Danielle A. E. ;
de Bruijn, Menno T. ;
Steller, Ernst J. A. ;
Emmink, Benjamin L. ;
Borel-Rinkes, Inne H. M. ;
Kranenburg, Onno .
CELLULAR ONCOLOGY, 2011, 34 (04) :307-313
[42]   p53-dependent regulation of Mcl-1 contributes to synergistic cell death by ionizing radiation and the Bcl-2/Bcl-XL inhibitor ABT-737 [J].
Katrin E. Tagscherer ;
Anne Fassl ;
Tabea Sinkovic ;
Stephanie E. Combs ;
Wilfried Roth .
Apoptosis, 2012, 17 :187-199
[43]   Synergistic Anticancer Effects of the 9.2.27PE Immunotoxin and ABT-737 in Melanoma [J].
Risberg, Karianne ;
Fodstad, Oystein ;
Andersson, Yvonne .
PLOS ONE, 2011, 6 (09)
[44]   Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B [J].
R W Rooswinkel ;
B van de Kooij ;
M Verheij ;
J Borst .
Cell Death & Disease, 2012, 3 :e366-e366
[45]   Resistance to ABT-737 in activated T lymphocytes: molecular mechanisms and reversibility by inhibition of the calcineurin-NFAT pathway [J].
Cippa, P. E. ;
Kraus, A. K. ;
Lindenmeyer, M. T. ;
Chen, J. ;
Guimezanes, A. ;
Bardwell, P. D. ;
Wekerle, T. ;
Wuethrich, R. P. ;
Fehr, T. .
CELL DEATH & DISEASE, 2012, 3 :e299-e299
[46]   Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins [J].
K E Tagscherer ;
A Fassl ;
B Campos ;
M Farhadi ;
A Kraemer ;
B C Böck ;
S Macher-Goeppinger ;
B Radlwimmer ;
O D Wiestler ;
C Herold-Mende ;
W Roth .
Oncogene, 2008, 27 :6646-6656
[47]   Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737 [J].
Renault, Thibaud T. ;
Teijido, Oscar ;
Missire, Florent ;
Ganesan, Yogesh Tengarai ;
Velours, Gisele ;
Arokium, Hubert ;
Beaumatin, Florian ;
Llanos, Raul ;
Athane, Axel ;
Camougrand, Nadine ;
Priault, Muriel ;
Antonsson, Bruno ;
Dejean, Laurent M. ;
Manon, Stephen .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2015, 64 :136-146
[48]   Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: In vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737 [J].
Ishitsuka, Kenji ;
Kunami, Naoko ;
Katsuya, Hiroo ;
Nogami, Rumiko ;
Ishikawa, Chie ;
Yotsumoto, Fusanori ;
Tanji, Hiroe ;
Mori, Naoki ;
Takeshita, Morishige ;
Miyamoto, Shingo ;
Tamura, Kazuo .
CANCER LETTERS, 2012, 317 (02) :218-225
[49]   The BCL-2 family protein inhibitor ABT-737 as an additional tool for the treatment of EBV-associated post-transplant lymphoproliferative disorders [J].
Robert, Aude ;
Pujals, Anais ;
Favre, Loetitia ;
Debernardi, Justine ;
Wiels, Joelle .
MOLECULAR ONCOLOGY, 2020, 14 (10) :2520-2532
[50]   Ionizing Radiation Sensitizes Breast Cancer Cells to Bcl-2 Inhibitor, ABT-737, through Regulating Mcl-1 [J].
Wu, Hao ;
Schiff, Devora S. ;
Lin, Yong ;
Neboori, Hanmanth J. R. ;
Goyal, Sharad ;
Feng, Zhaohui ;
Haffty, Bruce G. .
RADIATION RESEARCH, 2014, 182 (06) :618-625