Ethyl 2- [N-m-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01006) induces apoptosis in human cervical cancer HeLa cells.
Human cervical cancer is potentially lethal, and therefore the development of effective and tolerable therapeutic options is vital. In the present study, the in vitro effect of the synthetized compound JOT01006 (C21H20C1NO4) on human cervical epithelioid carcinoma cell line (HeLa) was examined. The results demonstrated that JOT01006 induced morphological changes and cytotoxicity (decreased the percentage of viable cells) in a dose-dependent manner. JOT01006 induced apoptosis which was analyzed by flow cytometric methods and confirmed by DAPI staining and DNA fragmentation analyzed by DNA gel electrophoresis. JOT01006 also induced reactive oxygen species (ROS) overproduction before causing endoplasmic reticulum (ER) stress which was also confirmed by the increased levels of Grp78 and Gadd153. Western blotting was selected to demonstrate that JOT010006 promoted p53, Bak, PARP, caspase-3 levels and decreased the levels of Bcl-2 and Bcl-xL. Our results also showed that JOT01006 also promoted caspase-12 production followed by apoptosis. The results also showed that JOT01006 inhibited the migration of HeLa cells potentially through inhibition of MMP-2 and -9.
Huang
An-Cheng
AC
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung Taiwan, ROC.
Lin
Tsung-Ping
TP
Weng
Yueh-Shan
YS
Ho
Yung-Tsuan
YT
Lin
Hui-Ju
HJ
Huang
Li-Jiau
LJ
Kuo
Sheng-Chu
SC
Chung
Jing-Gung
JG
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D024161:Collagen Type XI / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; C499319:COL11A2 protein, human; D002264:Carboxylic Acids; D024161:Collagen Type XI; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D005663:Furans; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C522416:ethyl 2-(N-m-chlorobenzyl- (2'-methyl)) anilino-4-oxo-4,5-dihydrofuran-3-carboxylate; D051742:Transcription Factor CHOP; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002118:Calcium