RRC ID |
41824
|
著者 |
Noguchi S, Hirashima N, Furuno T, Nakanishi M.
|
タイトル |
Remarkable induction of apoptosis in cancer cells by a novel cationic liposome complexed with a bcl-2 antisense oligonucleotide.
|
ジャーナル |
J Control Release
|
Abstract |
We reported recently a novel cationic cholesterol derivative with a hydroxyethylamino head group, cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine (I) for liposome-mediated gene transfection [FEBS Lett., 408 (1997) 232]. In the present paper we have studied whether this novel cationic liposome is prominent in nature to suppress cell growth of human cancer cells. Bcl-2 antisense phosphorothioate oligonucleotides (AS-ODNs) were complexed with the cationic liposomes with the derivative (I) and they were introduced into human cervix epithelial carcinoma cell lines HeLa, and mouse fibroblast NIH3T3 cells. An AS-ODNs targeting/bcl-2 gene induced probably apoptosis (including necrosis in some cases) in HeLa and NIH3T3 cells, however, nonsense oligonucleotides (NS-ODNs) corresponding to a scrambled-sequence control hardly induced apoptosis. Induction of apoptosis was much greater than that by commercially available DC-Chol liposomes. Fluorescence intensities of FITC-conjugated bcl-2 AS-ODNs were specifically found in the nucleus. The intensity of the AS-ODNs was mostly consistent with the amounts of Bcl-2 proteins observed by Western blot analysis in the target cells. The results showed the possibility that this new cationic cholesterol derivative might be very promising to be used for liposome-mediated gene targeting in vitro and in vivo.
|
巻・号 |
88(2)
|
ページ |
313-20
|
公開日 |
2003-3-7
|
DOI |
10.1016/s0168-3659(02)00484-4
|
PII |
S0168365902004844
|
PMID |
12628337
|
MeSH |
Apoptosis / drug effects*
Cations
DNA, Neoplasm / biosynthesis
DNA, Neoplasm / genetics
Flow Cytometry
Genes, Reporter / genetics
Genes, bcl-2 / genetics*
Humans
Immunoblotting
Liposomes
Luciferases
Microscopy, Confocal
Neoplasms / pathology*
Oligonucleotides, Antisense / administration & dosage*
Oligonucleotides, Antisense / pharmacology*
Tumor Cells, Cultured
|
IF |
7.727
|
引用数 |
13
|
WOS 分野
|
CHEMISTRY, MULTIDISCIPLINARY
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
HeLa(RCB0007)
NIH3T3 |