Limonin inhibits the stemness of cancer stem-like cells derived from colorectal carcinoma cells potentially via blocking STAT3 signaling  

作　　者：Wei-Feng Zhang Cheng-Wei Ruan Jun-Bo Wu Guo-Liang Wu Xiao-Gan Wang Hong-Jin Chen 

机构地区：[1]Department of Colorectal Surgery,The Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu Province,China [2]Department of Anorectal Section,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu Province,China [3]Department of Colorectal Surgery,Hengyang Central Hospital,Hengyang 421000,Hunan Province,China [4]The First College for Clinical Medicine,Nanjing University Of Chinese Medicine,Nanjing 210023,Jiangsu Province,China

出　　处：《World Journal of Clinical Oncology》2024年第2期317-328,共12页世界临床肿瘤学杂志（英文版）

摘　　要：BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal cancer(CRC)cells and cancer stem-like cells(CSCs),a subpopulation responsible for a poor prognosis,is unclear.AIM To evaluate the effects of limonin on CSCs derived from CRC cells.METHODS CSCs were collected by culturing CRC cells in serum-free medium.The cytotoxicity of limonin against CSCs and parental cells(PCs)was determined by cholecystokinin octapeptide-8 assay.The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.RESULTS As expected,limonin exerted inhibitory effects on CRC cell behaviors,including cell proliferation,migration,invasion,colony formation and tumor formation in soft agar.A relatively low concentration of limonin decreased the expression stemness hallmarks,including Nanog andβ-catenin,the proportion of aldehyde dehydrogenase 1-positive CSCs,and the sphere formation rate,indicating that limonin inhibits stemness without presenting cytotoxicity.Additionally,limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice.Moreover,limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression.Inhibition of Nanog andβ-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2μmol/L colievlin.CONCLUSION Taken together,these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

关 键 词：LIMONIN Colorectal cancer STAT3 signaling Cancer stem-like cells STAT3 Aldehyde dehydrogenase 1 

分 类 号：R73-36[医药卫生—肿瘤]