Extract of Codiaeum luzonicum Merr. overcomes multidrug resistance in human colon cancer cells by modulating P-glycoprotein

作     者：Regina Joyce E.Ferrer Marc Justin C.Ong Sonia D.Jacinto Regina Joyce E.Ferrer;Marc Justin C.Ong;Sonia D.Jacinto

作者机构：Institute of BiologyUniversity of the Philippines DilimanQuezon CityMetro ManilaPhilippines 

出 版 物：《Asian Pacific Journal of Tropical Biomedicine》 (亚太热带生物医学杂志（英文版）)

年 卷 期：2022年第12卷第9期

页      面：400-410页

核心收录：

学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：This work was supported by the University of the Philippines Diliman Office of the Vice Chancellor for Research and Development Outright Grant(grant number 151509 PNSE). 

主　　题：Natural product Leaf extract Codiaeum luzonicum MDR cancer P-gp inhibitor Colorectal cancer 

摘      要：Objective:To investigate anti-multidrug resistance(MDR)activity and safety of the bioactive fraction(CL11)from Codiaeum luzonicum crude leaf extract.Methods:Cytotoxic activity of CL11 against MDR and nonresistant colon cancer cells was assessed using MTT assay.Mode of cell death was investigated by annexin V-propidium iodide staining,TUNEL,and JC-1 assays.To examine mechanism of action,the effect on the expression and function of the MDR-implicated protein P-glycoprotein was tested using Western blotting and calcein assay,respectively.Results:CL11 had an EC50 of 0.18,1.03 and 38.52µg/mL against HCT-15,HCT-15/Dox and HCT116,respectively.Cytotoxicity was mediated by inhibition of P-glycoprotein function and expression.The mode of cell death involved mitochondrial membrane depolarization and was mostly non-apoptotic at EC50 concentrations against HCT-15 and HCT-15/Dox.Conclusions:Fraction CL11 of Codiaeum luzonicum induces nonapoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.