Journal
ANTI-CANCER DRUGS
Volume 28, Issue 6, Pages 634-644Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000000504
Keywords
adrenocortical carcinoma; AMG 900; aurora kinases; Notch signaling
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/08699-5, 10/07020-9]
- Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/07020-9, 10/08699-5] Funding Source: FAPESP
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Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis induction and acted synergistically with mitotane and doxorubicin in the inhibition of proliferation. In addition, we found that AMG 900 activated Notch signaling and rendered the cells sensitive to the combination of AMG 900 and Notch signaling inhibition. Altogether, these data show that aurora kinases inhibition using AMG 900 may be an adjuvant therapy to treat patients with invasive or recurrent adrenocortical carcinomas. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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