Ji Ho Yun1, Kyung-A Kim2, Gyhye Yoo3, Sun Young Kim4, Ji Min Shin5, Jung Hoon Kim6, Sang Hoon Jung7, Jungho Kim6, Chu Won Nho8. 1. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Department of Life Science, Sogang University, Seoul 04107, Korea. 2. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Daejeon 34113, Korea. 3. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea. 4. Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea. 5. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Daejeon 34113, Korea. 6. Department of Life Science, Sogang University, Seoul 04107, Korea. 7. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea. 8. Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea. Electronic address: cwnho@kist.re.kr.
Abstract
BACKGROUND: Cancer stem cells (CSCs) are a subset of cells within the bulk of a tumor that have the ability to self-renew and differentiate, and are thus associated with cancer invasion, metastasis, and recurrence. Phenethyl isothiocyanate (PEITC) is a natural compound found in cruciferous vegetables such as broccoli and is used as a cancer chemopreventive agent; however, its effects on CSCs are little known. PURPOSE: To evaluate the effect of PEITC on CSCs in this study by examining CSC properties. METHODS: NCCIT human embryonic carcinoma cells were treated with PEITC, and the expression of pluripotency factors Oct4, Sox-2, and Nanog were evaluated by luciferase assay and western blot. Effect of PEITC on self-renewal capacity and clonogenicity were assessed with the sphere formation, soft agar assay, and clonogenic assay in an epithelial cell adhesion molecule (EpCAM)-expressing CSC model derived from HCT116 colon cancer cells using a cell sorting system. The effect of PEITC was also investigated in a mouse xenograft model obtained by injecting nude mice with EpCAM-expressing cells. RESULTS: We found that PEITC treatment suppressed expression of the all three pluripotency factors in the NCCIT cells, in which pluripotency factors are highly expressed. Moreover, PEITC suppressed the self-renewal capacity and clonogenicity in the EpCAM-expressing CSC model. EpCAM was used as a specific CSC marker in this study. Importantly, PEITC markedly suppressed both tumor growth and expression of three pluripotency factors in a mouse xenograft model. CONCLUSION: These results demonstrate that PEITC might be able to slow down or prevent cancer recurrence by suppressing CSC stemness.
BACKGROUND:Cancer stem cells (CSCs) are a subset of cells within the bulk of a tumor that have the ability to self-renew and differentiate, and are thus associated with cancer invasion, metastasis, and recurrence. Phenethyl isothiocyanate (PEITC) is a natural compound found in cruciferous vegetables such as broccoli and is used as a cancer chemopreventive agent; however, its effects on CSCs are little known. PURPOSE: To evaluate the effect of PEITC on CSCs in this study by examining CSC properties. METHODS: NCCIT humanembryonic carcinoma cells were treated with PEITC, and the expression of pluripotency factorsOct4, Sox-2, and Nanog were evaluated by luciferase assay and western blot. Effect of PEITC on self-renewal capacity and clonogenicity were assessed with the sphere formation, soft agar assay, and clonogenic assay in an epithelial cell adhesion molecule (EpCAM)-expressing CSC model derived from HCT116 colon cancer cells using a cell sorting system. The effect of PEITC was also investigated in a mouse xenograft model obtained by injecting nude mice with EpCAM-expressing cells. RESULTS: We found that PEITC treatment suppressed expression of the all three pluripotency factors in the NCCIT cells, in which pluripotency factors are highly expressed. Moreover, PEITC suppressed the self-renewal capacity and clonogenicity in the EpCAM-expressing CSC model. EpCAM was used as a specific CSC marker in this study. Importantly, PEITC markedly suppressed both tumor growth and expression of three pluripotency factors in a mouse xenograft model. CONCLUSION: These results demonstrate that PEITC might be able to slow down or prevent cancer recurrence by suppressing CSC stemness.
Authors: Alena Liskova; Peter Kubatka; Marek Samec; Pavol Zubor; Milos Mlyncek; Tibor Bielik; Samson Mathews Samuel; Anthony Zulli; Taeg Kyu Kwon; Dietrich Büsselberg Journal: Molecules Date: 2019-03-04 Impact factor: 4.411