Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines.

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.

Antineoplastic effect of a novel nanosized curcumin on cutaneous T cell lymphoma.

Cutaneous T cell lymphomas (CTCLs) are a group of heterogeneous, life-threatening, extra-nodal and lymphoproliferative T cell neoplasms. Since chronic inflammation serves a key role in CTCL progression, curcumin, a natural pigment with proven anti-inflammatory and antineoplastic properties, as well as minimal toxicity, may be used as a therapeutic agent. In the present study, two formulations of curcumin (standard ethanolic and a Pluronic®P-123/F-127 micellar solution) were compared regarding their cytotoxic efficacy and speed of internalization in three CTCL cell lines, namely HuT-78, HH and MJ. In addition, the modulating effect of curcumin on selected proteins involved in the proliferation and progression of the disease was determined. The results indicated the superiority of the Pluronic®P-123/F-127 micellar curcumin over the standard ethanol solution in terms of cellular internalization efficiency as determined by spectrophotometric analysis. Notably, the presence of commonly used media components, such as phenol red, may interfere when interpreting the cytotoxicity of curcumin, due to their overlapping absorbance peaks. Therefore, it was concluded that phenol red-free media are superior over media with phenol red in order to correctly measure the cytotoxic efficacy and cell penetration of curcumin. Depending on the cell line, the IC50 values of micellar curcumin varied from 29.76 to 1.24 µΜ, with HH cells demonstrating the highest sensitivity. This cell line had the lowest expression levels of the Wilms' tumor-1 transcription factor. Performing western blot analyses of treated and untreated CTCL cells, selective signal transduction changes were recorded for the first time, thus making curcumin nano-formulation an attractive and prospective option with therapeutic relevance for CTCL as a rare orphan disease.