Isothiocyanate iberin modulates phase II enzymes, posttranslational modification of histones and inhibits growth of Caco-2 cells by inducing apoptosis.
The aim of presented study was to further investigate the concentration-dependent changes induced by isothiocyanate iberin (IBN) in human colon carcinoma Caco-2 cells. The concentrations of IBN below IC(50) value (18 microM, 72 h) triggered the augmentation of mRNA levels for phase II detoxification GSTA1 and UGT1A1 enzymes and antioxidant thioredoxin reductase 1 gene in cells treated for 24 h. In addition a significant increase of acetylated H4 histone was detected. The mRNA induction peaked at IC(50) value and returned to level of control cells at 40 microM concentration of IBN. The cell cycle changes, gamma-H2AX stainability and the increase of phospho-H3 mitotic marker were induced at concentrations above IC(50) value. Appearance of Annexin V positive apoptotic cells and sub-G1 fragmented DNA as well as decrease of mitochondrial transmembrane potential confirmed cytotoxic effect of IBN observed in MTT assay. The predominance of necrotic cells and profound positivity of gamma-H2AX took place at the highest concentration of IBN. Thus, IBN represents the effective member of natural chemopreventive isothiocyanate family with which apoptotic potential can by employed to eliminate tumor cells.
Jakubikova
J
J
Laboratory of Tumor Immunology, Cancer Research Institute, 833 91 Bratislava, Slovak Republic.
Bao
Y
Y
Bodo
J
J
Sedlak
J
J
D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D000099148:UGT1A1 Enzyme
D053148:Caspase 3; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D006657:Histones; D017879:Isothiocyanates; D010936:Plant Extracts; D012333:RNA, Messenger; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase; D000099148:UGT1A1 Enzyme; C468783:H2AX protein, human; C082585:iberin; C516124:TXNRD1 protein, human; C484555:GSTA1 protein, human