Evaluating the gene-expression profiles of HeLa cancer cells treated with activated and nonactivated poly(amidoamine) dendrimers, and their DNA complexes.
Using dendrimers in cancer therapy as nonviral vectors for gene delivery seems promising. The biological performance of a dendrimer-based gene delivery system depends heavily on its molecular architecture. The transfection activity of dendrimers is significantly improved by processes activated in the heat degradation treatment of solvolysis. However, very little is known about the molecular mechanisms that dendrimers produce in cancer cells. We studied the changes in global gene-expression profiles in human cervical cancer HeLa cells exposed to nonactivated and activated poly(amidoamine) (PAMAM) dendrimers, alone or in complexes with plasmid DNA (dendriplexes). Real-time quantitative reverse transcriptase-polymerase chain reaction was used to confirm four regulated genes (PHF5A, ARNTL2, CHD4, and P2RX7) affected by activated dendrimers and dendriplexes. Activated and nonactivated dendrimers and dendriplexes alike induced multiple gene expression changes, some of which overlapped with their dendriplexes. Dendrimer activation improved transfection efficiency and induced additional gene expression changes in HeLa cells. Dendrimers and dendriplexes principally affect genes with the molecular functions of nucleic acid binding and transcription activity, metal-ion binding, enzyme activity, receptor activity, and protein binding. Our findings provide a deeper insight into the changes in gene expression patterns caused by the molecular structure of PAMAM dendrimers for gene-based cancer therapy.
Kuo
Jung-hua Steven
JH
Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Sec. 1, Jen-Te, Tainan 717, Taiwan. kuojunghua@yahoo.com.tw
Liou
Meng-jie
MJ
Chiu
Hsueh-chen
HC
D056930:ARNTL Transcription Factors / Q000235:genetics; D001324:Autoantigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D050091:Dendrimers / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011073:Polyamines / Q000737:chemistry*; D016601:RNA-Binding Proteins; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058486:Receptors, Purinergic P2X7; D015534:Trans-Activators
D056930:ARNTL Transcription Factors; C486615:BMAL2 protein, human; D001324:Autoantigens; C115323:CHD4 protein, human; D002352:Carrier Proteins; D050091:Dendrimers; C546468:P2RX7 protein, human; C486761:PHF5A protein, human; C531249:Poly(amidoamine); D011073:Polyamines; D016601:RNA-Binding Proteins; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D015534:Trans-Activators; D004247:DNA; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex