Cancer-preventive effect of phenethyl isothiocyanate through tumor microenvironment regulation in a colorectal cancer stem cell xenograft model.

BACKGROUND: Phenethyl isothiocyanate (PEITC) is a glucosinolate derived from cruciferous vegetables and is a cancer-chemopreventive reagent. Cancer stem cells (CSCs) have roles in cancer chemoresistance, invasion, metastasis, and recurrence. Here, we investigated whether PEITC can suppress the properties of CSCs using NCCIT cells and HCT116-derived cancer stem-like cells. Furthermore, we established a CSC xenograft prevention model using nude mice. PURPOSE: The purpose of this study was to examine the actual cancer-preventive effects of PEITC in vitro and in a xenograft prevention model. STUDY DESIGN: We assessed the cancer-preventive effects of PEITC on CSCs using a novel xenograft prevention model. METHODS: NCCIT cells were treated with PEITC, and the expression of pluripotent markers was confirmed by reporter assays, western blotting, and qRT-PCR. In addition, to evaluate the effects of PEITC on CSC properties, sphere cells, which exhibit CSC properties, were established from the HCT116 cells. Furthermore, to examine the inhibitory effects and the underlying mechanism following daily intake of PEITC on CSCs, we performed an animal study in a mouse xenograft model and RNA-sequencing analysis. RESULTS: PEITC significantly reduced the CSC properties, including clonogenicity and the expression of pluripotent factors. Prior to CSC inoculation in vivo, the PEITC pre-treatment group showed a more effective reduction in the tumor growth rate and expression of CSC markers compared to the post-treatment groups. Furthermore, RNA-sequencing results showed that PEITC pre-treatment remarkably suppressed genes related to inflammatory and immune responses and chemokine-related signaling. CONCLUSION: PEITC might contribute to the prevention or delay of colorectal cancer growth by inhibiting CSCs via the regulation of inflammatory chemokines, which can affect the tumor microenvironment. Thus, our study suggests that the daily intake of phytochemicals derived from vegetables or dietary supplements could have cancer-preventive effects through regulation of the host-tumor microenvironment.

Comparative release kinetics of small drugs (ibuprofen and acetaminophen) from multifunctional mesoporous silica nanoparticles.

Multifunctional mesoporous silica nanoparticles (MSNs) can confer dynamically varied release kinetics depending on the intermolecular interactions between model drugs and functional decorations on the MSNs. Herein, brush-like fluorescent conjugates were grafted on the pore walls of pristine MSNs for high drug loading and to impart fluorescence properties. The fluorescent MSNs (FMSNs) were further coated with polydopamine (PDA) and graphene oxide (GO) double layer, designated FMSNs@PDA and FMSNs@PDA@GO, respectively. The FMSNs@PDA@GO exhibited highly consistent drug release over one week (∼7 days) because of the consolidated PDA/GO double layer at neutral pH (7.4). However, the release rate of FMSN-Ibu@PDA@GO was increased at acidic pH (5.5) because the PDA/GO double layer was partially disrupted due to weakened π-π stacking and electrostatic interactions. The release kinetics of the FMSNs-based NPs (FMSNs, FMSNs@PDA, and FMSNs@PDA@GO) were systematically investigated using negatively charged hydrophobic ibuprofen and neutral hydrophilic acetaminophen at pH 7.4. In the FMSN-drug system, the release rate of acetaminophen was higher than that of ibuprofen because of the higher solubility of acetaminophen in aqueous solution. In addition, ibuprofen has a bulky molecular structure compared to acetaminophen, leading to its slower transmission through the porous channels of FMSNs. In the FMSNs-drug@PDA system, acetaminophen exhibited a slower release rate than ibuprofen, owing to the π-π stacking interactions in the transmission of neutral acetaminophen by the PDA coating layer. On the other hand, the FMSNs-drug@PDA@GO exhibited a slower ibuprofen release rate than acetaminophen, owing to the electrostatic repulsion effect of the negative GO layer. Our drug delivery system was demonstrated as an advanced delivery platform, in which the transmission rate is controlled by intermolecular interactions between the diffusing drugs and functional decorations on the nanocarrier.