Suppression of apoptosis in hepatocytes by fructose‐modified dendrimers

Kawase, Masaya; Shiomi, T.; Matsui, Hisaji; Ouji, Yukiteru; Higashiyama, Shigeki; Tsutsui, Takahiro; Yagi, K.

doi:10.1002/1097-4636(20010315)54:4<519::aid-jbm70>3.3.co;2-r

Cited by 5 publications

(7 citation statements)

References 7 publications

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“…This information is vital for the development of safe clinical applications. To date, only one research group has shown that the cytotoxicity induced by PAMAM dendrimers in hepatocytes was characterized by apoptosis (Kawase et al 2001;Higashiyama et al 2003). In the present study, we found that starburst PAMAM and DAB dendrimers could cause apoptosis in cultured macrophage cells.…”

Section: Discussionsupporting

confidence: 56%

“…To date, only one research group has shown that the cytotoxicity induced by PAMAM dendrimers in hepatocytes was characterized by apoptosis (Kawase et al 2001;Higashiyama et al 2003). Therefore, a better understanding of the mechanisms of cell death induced by cationic dendrimers is necessary for the further development of appropriate delivery systems.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage-like cells

Kuo

Jan

Chiu

2005

Journal of Pharmacy and Pharmacology

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Cationic dendrimers possess attractive nano-sized architectures that make them suitable as targeted drug/gene delivery systems. However, very little is known about their mechanisms of cell death in cellular systems. In the current study, the apoptotic and necrotic effects of starburst polyamidoamine(PAMAM) and polypropylenimine (DAB) dendrimers in cultured RAW 264.7 murine macrophage-like cells were investigated. Cationic dendrimer treatment produced a typically dose-dependent cytotoxic effect on macrophage cells. RAW 264.7 cells exposed to cationic dendrimers exhibited morphological features of apoptosis. Apoptotic ladders were observed in DNA extracted from RAW 264.7 cells treated with cationic dendrimers. Analysis from flow cytometry demonstrated an increase in hypodiploid DNA population (sub-G1) and a simultaneous decrease in diploid DNA content, indicating that DNA cleavage occurred after exposure of the cells to cationic dendrimers. Also, cells treated with DAB dendrimer induced a higher percentage of sub-G1 population than those treated with PAMAM dendrimer at the same dose. In addition, it was shown that pre-treatment of RAW 264.7 cells with the general caspase inhibitor zVAD-fmk prevented some degree of apoptosis induced by cationic dendrimers, suggesting that apoptosis in macrophage cells involves a caspase dependent pathway. Macrophage cells were also found to be sensitive to induction of apoptosis by dendrimers, whereas NIH/3T3 cells (mouse fibroblast) and BNL CL.2 (mouse liver) cells did not undergo apoptosis. These results could be helpful for optimizing the biocompatibility of dendrimers used for targeted drug/gene delivery.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage-like cells

Kuo

Jan

Chiu

2005

Journal of Pharmacy and Pharmacology

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“…Dendrimers are novel, highly versatile molecules that have found application in a variety of biological and biomedical applications. Dendrimers have been studied as gene (Haenseler and Szoka (1993); Kukowska-Latallo et al, (1996); Bielinska et al, (1997); Bielinska et al, (1999); Bielinska et al, (2000)) and drug delivery (Barth et al, (1994); Kono et al, (1999); Liu et al, (2000); ; ) vehicles, as well as for cellular recognition, cell adhesion and cell growth regulation (Zanini et al (1995); Zanini and Roy (1997); Kawase et al (2001)). They have also been used for the modification of biologically relevant polymeric materials to increase the density of relevant functional groups (Duan et al (2002)).…”

Section: Introductionmentioning

confidence: 99%

Partitioning of model toxins to hydrophobically terminated DAB dendrimers

King

Duan

Sheardown

2004

Biotech & Bioengineering

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Dendrimers are attractive in biological and biomedical applications due to the similarity in their molecular size to biologically relevant molecules and the large number of chain ends available functionalization. In the current work, we examined the potential of diamino butane (DAB) dendrimers functionalized with long alkyl chains as partitioning agents for hydrophobic toxins for use as a prefiltering stage in a bioartiticial liver. DAB dendrimers of various generations that had been previously fully modified with palmitoyl chloride were obtained. A study of the kinetics of partitioning of acetylsalicylic acid (ASA) suggested that while significant toxin removal occurred in 30 s, although a slight time dependent increase in removal was noted up to 60 minutes. The partitioning of 6 hydrophobic toxins from aqueous solution to the modified dendrimers in 30 minutes was examined. The results demonstrated that a number of factors, including the pKa of the toxin, its octanol water partitioning coefficient and molecular size contributed to the level of toxin removal. Toxin removal on a molar basis increased with increasing dendrimer generation for all toxins, with the modified G5 dendrimers partitioning 50 -100 toxin molecules in most cases. Dendrimer modification with C4 alkyl chains rather than Cl5 chains significantly decreased toxin removal, although chains longer than C10 seemed to partition equal amounts of toxins. The results of the study demonstrate that water-soluble dendrimers modified with hydrophobic end groups may be useful for the removal of toxins from the blood in a prereaction step for a bioartificial liver, but that a better understanding of the molecular mechanisms of removal may be necessary before it is possible to predict the levels of toxin removal. B 2004 Wiley Periodicals, Inc.

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“…29) To date, there are only a few reports concerning dendrimer-induced apoptosis. It has been showed that PAMAM dendrimers could cause apoptosis in hepatocytes 30) and in cultured RAW 264.7 murine macrophage-like cells. 31) Kuo et al have found that RAW 264.7 macrophage cells were sensitive to induction of apoptosis by PAMAM and DAB dendrimers, whereas mouse fibroblasts NIH/3T3 and mouse liver BNL CL.2 cells did not undergo apoptosis.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Generation 2 and 3 Poly(amidoamine) Dendrimers on Viability of Human Breast Cancer Cells

Winnicka¹,

Bielawski²,

Rusak

et al. 2009

JOURNAL OF HEALTH SCIENCE

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In this study, we investigated the effect of amine-and hydroxyl-terminated Generation 2 and 3 (G2 and G3) poly(amidoamine) (PAMAM) dendrimers on the viability and induction of apoptosis in human MCF-7 and MDA-MB-231 breast cancer cells. It was shown that amino-terminated PAMAM dendrimers were cytotoxic, with IC 50 value after 24 hr of incubation in MCF-7 and MDA-MB-231 breast cancer cells 153 ± 3 µM and 140 ± 2 µM for G2 PAMAM and 120 ± 3 µM and 99 ± 2 µM for G3 PAMAM, respectively. Experiments made with annexin V-fluorescein isothiocyanate (V-FITC) and detection of apoptosis by a fluorescent microscopy assay revealed that G2 and G3 PAMAM-NH 2 dendrimers inhibited the proliferation of MCF-7 and MDA-MB-231 malignant cells by increasing the number of apoptotic and necrotic cells. The cytotoxic and apoptotic effect of G2 and G3 PAMAM-OH dendrimers was significantly weaker.

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Suppression of apoptosis in hepatocytes by fructose‐modified dendrimers

Cited by 5 publications

References 7 publications

Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage-like cells

Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage-like cells

Partitioning of model toxins to hydrophobically terminated DAB dendrimers

The Effect of Generation 2 and 3 Poly(amidoamine) Dendrimers on Viability of Human Breast Cancer Cells

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