Shin, Ji Min Lim, Eunbi Cho, Yoon Shin Nho, Chu Won 2024-01-19T15:03:19Z 2024-01-19T15:03:19Z 2021-09-05 2021-04 0944-7113 https://pubs.kist.re.kr/handle/201004/117218 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. English ELSEVIER GMBH Cancer-preventive effect of phenethyl isothiocyanate through tumor microenvironment regulation in a colorectal cancer stem cell xenograft model Article 10.1016/j.phymed.2021.153493 1 PHYTOMEDICINE, v.84 PHYTOMEDICINE 84 scie scopus 000627864600008 2-s2.0-85101386882 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Pharmacology & Pharmacy Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article APOPTOSIS CXCL3 DEATH ERK Phenethyl isothiocyanate Cancer stem cell Cancer prevention Xenograft model Tumor microenvironment