Comparison of the Effects of Monastrol and Oxomonastrol on Human Hepatoma Cell Line HepG2/C3A.
Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels. However, oxomonastrol was cytotoxic only at the highest concentrations used, without reducing cell proliferation and viability. Moreover, no genotoxic damage or alteration of levels of mRNA were found. Our results suggest that monastrol has greater antiproliferative activity compared to oxomonastrol, and this effect is probably related to the DNA damage induced by monastrol and its possible bioactivation demonstrated by the increase in CYP1A1 mRNA expression. Moreover, these effects appear to be related to the presence of the sulfur atom in its structure.
General Biology Department, State University of Londrina, Londrina, Brazil lilian.areal.marques@gmail.com.
Lilian Areal
LA
Marques
General Biology Department, State University of Londrina, Londrina, Brazil.
Simone Cristine
SC
Semprebon
General Biology Department, State University of Londrina, Londrina, Brazil.
Daniele
D
Sartori
Chemistry Department, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Ângelo
Â
DE Fátima
Pathology Department, Júlio de Mesquita Filho State University of São Paulo, Botucatu, Brazil.
Lúcia Regina
LR
Ribeiro
General Biology Department, State University of Londrina, Londrina, Brazil.
Mário Sérgio
MS
Mantovani
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects; D013871:Thiones / Q000494:pharmacology*
D011743:Pyrimidines; D011744:Pyrimidinones; D012333:RNA, Messenger; D013871:Thiones; C000616961:oxomonastrol; C400223:monastrol; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1
CYP1A1; EG5; Monastrol; anticancer; oxomonastrol