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Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines.

Haririan I, Alavidjeh MS, Khorramizadeh MR, Ardestani MS, Ghane ZZ, Namazi H - Int J Nanomedicine (2010)

Bottom Line: Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers.In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results.In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. haririan@tums.ac.ir

ABSTRACT
Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers. In this report, two conjugates (G1+Pt and G2+Pt) of cisplatin [cis-diaminedichloroplatinum; (CDDP)] with two generations (G1, G2) of a biocompatible anionic dendrimer were prepared in an aqueous media. Their potential cytotoxic effects, in two sensitive cancer cell lines HT1080 and CT26 together with one resistant cancer cell line SKOV3, using MTT (methyl thiazolyl tetrazolium) assay were examined. Hemolytic impacts and cell death mechanisms of the conjugates on human blood and HT1080 cell line were also investigated. The conjugate G2+Pt showed greater toxicity up to 9x and 2x in the sensitive and resistant cell lines (IC(50) comparison, inhibitory concentration) respectively when compared to the parent drug. The G1+Pt conjugate showed greater toxicity only in the sensitive HT1080 (2x) and CT26 (3.7x) cell lines. Moreover, the G1+Pt conjugate was less toxic approximately one third of the cisplatin in SKOV3 after 48 hrs of incubation. In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results. Approximately the same hemolysis behavior was observed for both conjugates and cisplatin. Both apoptosis and necrosis mechanisms (about 2x more than cisplatin) were attributed to conjugates and cisplatin in a direct correlation between the concentration and the degree of cell death. In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.

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Viability of the different cancer cell lines according to the mitochondrial activity of the cells incubating with different kinds of Pt derivatives and free cisplatin (CDDP) after 24 and 48 hrs. (A) HT1080 cell line, (B) CT26 cell line, (c) SKOV3.
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f5-ijn-5-063: Viability of the different cancer cell lines according to the mitochondrial activity of the cells incubating with different kinds of Pt derivatives and free cisplatin (CDDP) after 24 and 48 hrs. (A) HT1080 cell line, (B) CT26 cell line, (c) SKOV3.

Mentions: As can be seen from Figure 5, the G2+Pt conjugate was more toxic than the parent cisplatin in all cell lines, times, and concentration range. The cytotoxic strength of some conjugates like G2+Pt based on IC50 calculation (the concentration which inhibits 50% growth against the maximum amount) with nonlinear regression (GraphPad,® version 4) was 9 × greater in HT1080 (24 hrs) and CT26 (48 hrs) cell lines in comparison with free cisplatin while the conjugate G1+Pt showed a higher maximum toxicity of 3.7 × in CT26 cell line in comparison with the cisplatin after 48 hrs of incubation. In addition, the G1+Pt showed less toxicity in SKOV3 cell line increased to one third of free cisplatin after 48 hrs of incubation, while the same potency was observed for SKOV3 and free cisplatin after 24 hrs of incubation. The G1+Pt also showed less toxicity in CT26 cell line after 24 hrs of incubation. The IC50 values are displayed in Figure 6.


Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines.

Haririan I, Alavidjeh MS, Khorramizadeh MR, Ardestani MS, Ghane ZZ, Namazi H - Int J Nanomedicine (2010)

Viability of the different cancer cell lines according to the mitochondrial activity of the cells incubating with different kinds of Pt derivatives and free cisplatin (CDDP) after 24 and 48 hrs. (A) HT1080 cell line, (B) CT26 cell line, (c) SKOV3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2819903&req=5

f5-ijn-5-063: Viability of the different cancer cell lines according to the mitochondrial activity of the cells incubating with different kinds of Pt derivatives and free cisplatin (CDDP) after 24 and 48 hrs. (A) HT1080 cell line, (B) CT26 cell line, (c) SKOV3.
Mentions: As can be seen from Figure 5, the G2+Pt conjugate was more toxic than the parent cisplatin in all cell lines, times, and concentration range. The cytotoxic strength of some conjugates like G2+Pt based on IC50 calculation (the concentration which inhibits 50% growth against the maximum amount) with nonlinear regression (GraphPad,® version 4) was 9 × greater in HT1080 (24 hrs) and CT26 (48 hrs) cell lines in comparison with free cisplatin while the conjugate G1+Pt showed a higher maximum toxicity of 3.7 × in CT26 cell line in comparison with the cisplatin after 48 hrs of incubation. In addition, the G1+Pt showed less toxicity in SKOV3 cell line increased to one third of free cisplatin after 48 hrs of incubation, while the same potency was observed for SKOV3 and free cisplatin after 24 hrs of incubation. The G1+Pt also showed less toxicity in CT26 cell line after 24 hrs of incubation. The IC50 values are displayed in Figure 6.

Bottom Line: Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers.In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results.In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. haririan@tums.ac.ir

ABSTRACT
Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers. In this report, two conjugates (G1+Pt and G2+Pt) of cisplatin [cis-diaminedichloroplatinum; (CDDP)] with two generations (G1, G2) of a biocompatible anionic dendrimer were prepared in an aqueous media. Their potential cytotoxic effects, in two sensitive cancer cell lines HT1080 and CT26 together with one resistant cancer cell line SKOV3, using MTT (methyl thiazolyl tetrazolium) assay were examined. Hemolytic impacts and cell death mechanisms of the conjugates on human blood and HT1080 cell line were also investigated. The conjugate G2+Pt showed greater toxicity up to 9x and 2x in the sensitive and resistant cell lines (IC(50) comparison, inhibitory concentration) respectively when compared to the parent drug. The G1+Pt conjugate showed greater toxicity only in the sensitive HT1080 (2x) and CT26 (3.7x) cell lines. Moreover, the G1+Pt conjugate was less toxic approximately one third of the cisplatin in SKOV3 after 48 hrs of incubation. In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results. Approximately the same hemolysis behavior was observed for both conjugates and cisplatin. Both apoptosis and necrosis mechanisms (about 2x more than cisplatin) were attributed to conjugates and cisplatin in a direct correlation between the concentration and the degree of cell death. In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.

Show MeSH
Related in: MedlinePlus