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

IF 1.7 4区医学 Q3 TROPICAL MEDICINE

Asian Pacific journal of tropical biomedicine Pub Date : 2022-09-01 DOI:10.4103/2221-1691.354431

R. Ferrer, Marc Ong, S. Jacinto

{"title":"Extract of Codiaeum luzonicum Merr. overcomes multidrug resistance in human colon cancer cells by modulating P-glycoprotein","authors":"R. Ferrer, Marc Ong, S. Jacinto","doi":"10.4103/2221-1691.354431","DOIUrl":null,"url":null,"abstract":"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 non- resistant 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 38.52 μg/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 non- apoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.","PeriodicalId":8560,"journal":{"name":"Asian Pacific journal of tropical biomedicine","volume":"12 1","pages":"400 - 410"},"PeriodicalIF":1.7000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Pacific journal of tropical biomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/2221-1691.354431","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TROPICAL MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

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 non- resistant 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 38.52 μg/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 non- apoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.

查看原文本刊更多论文

羽扇豆提取物。通过调节P-糖蛋白克服人结肠癌癌症细胞的多药耐药性

目的：研究羽扇豆叶提取物生物活性部分（CL11）的抗多药耐药性（MDR）活性及安全性。方法：应用MTT法检测CL11对多药耐药和非耐药结肠癌细胞的细胞毒性。通过膜联蛋白V碘化丙啶染色、TUNEL和JC-1测定来研究细胞死亡模式。为了检测作用机制，分别使用蛋白质印迹法和钙黄绿素测定法检测对MDR相关蛋白P-糖蛋白的表达和功能的影响。结果：CL11对HCT-15、HCT-15/Dox和HCT116的EC50分别为0.18、1.03和38.52μg/mL。细胞毒性是通过抑制P-糖蛋白的功能和表达来介导的。细胞死亡模式涉及线粒体膜去极化，并且在针对HCT-15和HCT-15/Dox的EC50浓度下大多是非凋亡的。结论：陆参组分CL11通过抑制P-糖蛋白的表达和功能来克服MDR，从而诱导MDR癌症细胞的非凋亡细胞死亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Asian Pacific journal of tropical biomedicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)

CiteScore

3.10

自引率

11.80%

发文量

2056

审稿时长

4 weeks

期刊介绍： The journal will cover technical and clinical studies related to health, ethical and social issues in field of biology, bacteriology, biochemistry, biotechnology, cell biology, environmental biology, microbiology, medical microbiology, pharmacology, physiology, pathology, immunology, virology, toxicology, epidemiology, vaccinology, hematology, histopathology, cytology, genetics and tropical agriculture. Articles with clinical interest and implications will be given preference.