Effect of imipramine on HT-29 cells’ proliferation, cell cycle arrest and apoptosis and its mechanism
World Chinese Journal of Digestology(2008)
Abstract
AIM: To investigate the effect of imipramine on cell growth, cell cycle and apoptosis of HT-29 colon cancer cells, and to elucidate its molecular mechanism. METHODS: Human colon cancer HT-29 cells were grown with routine cell cultivation and cells were treated with different concentrations of imiprmine. Cell survival was determined us-ing MTT assay at 24 h, 48 h and 72 h, respective-ly; cell cycle distribution was assessed by FACS flow cytometery after propidium iodide stain-ing; apoptosis of HT-29 cells was detected using Annexin V/PI methods and DNA ladder assay.Expression level of Eag1 protein was detected by Western blot, and mRNA expressions of p21, p27, CyclinE1 and CDK2 were determined by reverse transcription-polymerase chain reaction. RESULTS: After treatment with imipramine in HT-29 cells at 24, 48 and 72 h, IC50 were 43, 32 and 22 μmol/L, respectively. Cell viability decreased dose-dependently and time-depend-ently after treatment with imiprmince in HT 29 cells. Cell cycle arrested during the G0/G1 phase accompanied by the induction of apoptosis in a dose-dependent manner. With imipramine increasing, HT-29 cells apoptosis index gradu-ally increased (P < 0.01). Expression level of Eag1 protein was decreased in a dose-dependent manner (P < 0.05). The p21 mRNA and p27 mRNA were up-regulated (P < 0.05), and CDK2 mRNA and CyclinE1 mRNA were suppressed in imipramine-treated HT-29 cells in a dose-dependent manner (P < 0.05). CONCLUSION: Imipramine, a non-specific in-hibitor of Eag1 potassium channel, induces cell growth inhibition, cell-cycle arrest and apopto-sis in HT-29 cells through up-regulation of p27 and/or p21.
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Key words
Imipramine,Apoptosis,Ether à go-go,Cell-cycle,Colorectal cancer,Potassium channels
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