Induction of apoptosis in cancer cells through N-acetyl-l-leucine-modified polyethylenimine-mediated p53 gene delivery

Colloids and Surfaces. B, Biointerfaces
Zhiyuan LiQuanshun Li

Abstract

Herein, N-acetyl-L-leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine(2000). Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential ...Continue Reading

References

May 1, 2004·Trends in Pharmacological Sciences·Lorne J HofsethCurtis C Harris
Jul 30, 2005·Nature Reviews. Drug Discovery·Daniel W PackPatrick S Stayton
Oct 16, 2007·Cancer Cell·Thierry Soussi, Klas G Wiman

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Citations

Feb 8, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ramalingam VaikundamoorthyRajaram Rajendran
Aug 15, 2015·Biochemical and Biophysical Research Communications·Rainer TietzeChristoph Alexiou
May 28, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jie LiuPeihong Ni

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