TY  - JOUR
AU  - Trochopoulos, Antonios G X
AU  - Ilieva, Yana
AU  - Kroumov, Alexander D
AU  - Dimitrova, Lyudmila L
AU  - Pencheva-El Tibi, Ivanka
AU  - Philipov, Stanislav
AU  - Berger, Martin
AU  - Najdenski, Hristo M
AU  - Yoncheva, Krassimira
AU  - Konstantinov, Spiro M
AU  - Zaharieva, Maya M
TI  - Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines.
JO  - Pharmaceutics
VL  - 14
IS  - 12
SN  - 1999-4923
CY  - Basel
PB  - MDPI
M1  - DKFZ-2022-03179
SP  - 2688
PY  - 2022
AB  - Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity. Pharmacokinetic analysis showed that the micellar curcumin (MCRM) used in our study was characterized by low zeta potential, slow release of curcumin, and fast cell membrane penetration. The combination ratio 1:4 [erufosine:MCRM] achieved strong synergism by inhibiting cell proliferation and clonogenicity. The combined antiproliferative effects were calculated using the symbolic mathematical software MAPLE 15. The synergistic combination strongly decreased the expression of TWIST1 and protein kinase B/Akt as proven by western blotting. Significant reductions in NF-κB activation, induction of apoptosis, and altered glutathione levels were demonstrated by corresponding assays. In addition, the synergistic combination enhanced the anti-staphylococcal activity and prevented biofilm formation, as shown by crystal violet staining. Taken together, the above results show that the development of nanotechnological treatment modalities for CTCL, based on rational drug combinations exhibiting parallel antineoplastic and antibacterial effects, may prove efficacious.
KW  - TWIST1 (Other)
KW  - curcumin (Other)
KW  - cutaneous T-cell lymphoma (Other)
KW  - erufosine (Other)
KW  - nanotechnology (Other)
KW  - synergy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36559182
C2  - pmc:PMC9781439
DO  - DOI:10.3390/pharmaceutics14122688
UR  - https://inrepo02.dkfz.de/record/186458
ER  -