Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of the p15 gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin- exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 μM curcumin caused hypomethylation of the p15 promoter after six days. Hypomethylation of p15 was further found to be favoured by downregulation of DNA methyltransferase 1 after 10 μM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of the p15 promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 μM) for six days led to the up-regulation of p15 and down-regulation of DNA methyltransferase 1. Furthermore, curcumin- mediated reversal of p15 promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells.

• MeSH
• akutní lymfatická leukemie patologie   MeSH
• antitumorózní látky fytogenní farmakologie   toxicita   MeSH
• apoptóza účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• DNA-(cytosin-5-)methyltransferasa biosyntéza   genetika   MeSH
• down regulace účinky léků   MeSH
• enzymová indukce účinky léků   MeSH
• inhibitor p15 cyklin-dependentní kinasy biosyntéza   genetika   MeSH
• kurkumin farmakologie   toxicita   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• metylace DNA účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• nestabilita genomu účinky léků   MeSH
• promotorové oblasti (genetika) účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese u leukemie účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zlomy chromozomů účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH