title: Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness.
abstract: Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133⁺CD44⁺ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. dlwltn233@naver.com.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. tidygirlss@naver.com.
authors.forename: Yoo-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. s3hun@skku.edu.
authors.forename: JaeHwan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, Korea. heosc3@brmh.org.
authors.forename: Seung Chul
authors.initials: SC
authors.lastname: Heo
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul 07061, Korea. kllee@brmh.org.
authors.forename: Kook Lae
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Chaum Life Center, CHA University, Seoul 06062, Korea. sangwoon.choi@gmail.com.
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. yuri.kim@ewha.ac.kr.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
mesh_terms: D016588:Anticarcinogenic Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002392:Catechin / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002726:Chlorogenic Acid / Q000032:analysis / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004610:Ellagic Acid / Q000032:analysis / Q000378:metabolism; D005707:Gallic Acid / Q000032:analysis / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D031324:Juglans / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009754:Nuts / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D056910:Republic of Korea; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D010936:Plant Extracts; D004610:Ellagic Acid; D002726:Chlorogenic Acid; D005707:Gallic Acid; D002392:Catechin
keywords: bioactive compounds; cancer stem cells; colon cancer; self-renewal capacity; walnut phenolic extract