TY  - JOUR
A1  - Linder, Benedikt
A1  - Köhler, Leonhard H. F.
A1  - Reisbeck, Lisa
A1  - Menger, Dominic
A1  - Subramaniam, Dharmalingam
A1  - Herold-Mende, Christel
A1  - Anant, Shrikant
A1  - Schobert, Rainer
A1  - Biersack, Bernhard
A1  - Kögel, Donat
T1  - A new pentafluorothio-substituted curcuminoid with superior antitumor activity
T2  - Biomolecules
N2  - A new and readily available pentafluorothiophenyl-substituted N-methyl-piperidone curcuminoid 1a was prepared and investigated for its anti-proliferative, pro-apoptotic and cancer stem cell-differentiating activities against a panel of human tumor cell lines derived from various tumor entities. The compound 1a was highly anti-proliferative and reached IC50 values in the nanomolar concentration range. 1a was superior to the known anti-tumorally active curcuminoid EF24 (2) and its known N-ethyl-piperidone analog 1b in all tested tumor cell lines. Furthermore, 1a induced a noticeable increase of intracellular reactive oxygen species in HT-29 colon adenocarcinoma cells, which possibly leads to a distinct increase in sub-G1 cells, as assessed by cell cycle analysis. A considerable activation of the executioner-caspases 3 and 7 as well as nuclei fragmentation, cell rounding, and membrane protrusions suggest the triggering of an apoptotic mechanism. Yet another effect was the re-organization of the actin cytoskeleton shown by the formation of stress fibers and actin aggregation. 1a also caused cell death in the adherently cultured glioblastoma cell lines U251 and Mz54. We furthermore observed that 1a strongly suppressed the stem cell properties of glioma stem-like cell lines including one primary line, highlighting the potential therapeutic relevance of this new compound.
KW  - curcumin
KW  - piperidone
KW  - pentafluorothio group
KW  - fluorine
KW  - anticancer agents
KW  - cell death
KW  - glioblastoma
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62463
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-624637
SN  - 2218-273X
N1  - This work was financially supported by the National Institute of health (grant R01CA190291) and the Thomas O’Sullivan Foundation (S.A.). B.B. thanks Bayern Innovativ for a grant (2014-2668-SI-01/1).
VL  - 11
IS  - 7, art. 947
SP  - 1
EP  - 17
PB  - MDPI
CY  - Basel
ER  -