TY  - JOUR
A1  - Ritter, Andreas Hans
A1  - Friemel, Alexandra
A1  - Kreis, Nina-Naomi
A1  - Louwen, Frank
A1  - Yuan, Juping
T1  - Impact of Polo-like kinase 1 inhibitors on human adipose tissue-derived mesenchymal stem cells
T2  - Oncotarget
N2  - Polo-like kinase 1 (Plk1) has been established as one of the most promising targets for molecular anticancer intervention. In fact, various Plk1 inhibitors have been identified and characterized. While the data derived from the bench are prospective, the clinical outcomes are less encouraging by showing modest efficacy. One of the explanations for this discrepancy could be unintendedly targeting of non-malignant cells by Plk1 inhibitors. In this work, we have addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal stem cells (ASCs). We show that both visceral and subcutaneous ASCs display monopolar spindles, reduced viability and strong apoptosis induction upon treatment with BI 2536 and BI 6727, the Plk1 kinase domain inhibitors, and with Poloxin, the regulatory Polo-box domain inhibitor. While Poloxin triggers quickly apoptosis, BI 2536 and BI 6727 result in mitotic arrest in ASCs. Importantly, survived ASCs exhibit DNA damage and a pronounced senescent phenotype. In addition, Plk1 inhibition impairs ASCs’ motility and homing ability. These results show that Plk1 inhibitors target slowly proliferating ASCs, an important population of anti-inflammation and immune modulation. The toxic effects on primary cells like ASCs could be partially responsible for the reported moderate antitumor activity in patients treated with Plk1 inhibitors.
KW  - adipose tissue-derived stem cell
KW  - Plk1 inhibitors
KW  - mitotic arrest
KW  - apoptosis
KW  - senescence
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45837
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458377
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 51
SP  - 84271
EP  - 84285
PB  - Impact Journals LLC
CY  - [S.l.]
ER  -