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

Abstract

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 IC 50 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.

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

“…The released amount of CRM is obviously not sufficient to achieve the desired effect for this incubation period (24 h). In contrast, according to published data, 80 µM of pure CRM or CRM loaded in nanoparticles with rapid release significantly inhibits the activity of NF-κB [41,76,82,83]. In this regard, we could assume that not the gradual administration of low CRM doses over time but the fast release of higher doses in the first hours after treatment is crucial for the NF-κB inhibition.…”

Curcumin in treatment of hematological cancers: Promises and challenges

“… 101 Based on these studies, nanocarriers are capable of targeted delivery of curcumin at tumor site and they suppress lymphoma proliferation by inducting apoptosis. 134 More experiments are required to investigate role of other nanoparticles in delivery of curcumin for lymphoma suppression. Since curcumin potential in lymphoma suppression has been improved significantly through application of nanoparticles, a gap in the field is lack of studies about co-delivery of curcumin with siRNA, shRNA or CRISPR in synergistic lymphoma inhibition.…”

Transcriptomic and proteomic analysis of tumor suppressive effects of GZ17-6.02 against mycosis fungoides

“…Curcumin is a component of the dietary spice turmeric that has demonstrated anti-neoplastic effects through inhibition of the phosphoinositide 3-kinase (Pi3K)-Akt pathway, epidermal growth factor receptor (EGFR) signaling, vascular endothelial growth factor (VEGF), and matrix metalloproteases, as well as by promoting caspase and mitochondria-driven apoptosis 27 – 32 . Additionally, curcumin has been shown to induce apoptosis in CTCL cells, believed to be due to the inhibition of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT)3 signaling 33 , 34 . Similarly, harmine is shown to inhibit extracellular signal-regulated kinase (ERK) and Akt signaling and to disrupt EGFR activity by suppressing the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase, DYRK1A 35 – 37 .…”