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Inhibitory Effects of the Ruthenium Complex KP1019 in Models of Mammary Cancer Cell Migration and Invasion.

Bergamo A, Masi A, Jakupec MA, Keppler BK, Sava G - Met Based Drugs (2009)

Bottom Line: The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects.The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development.These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.

View Article: PubMed Central - PubMed

Affiliation: Callerio Foundation Onlus, Via A. Fleming 22-31, 34127 Trieste, Italy.

ABSTRACT
The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects. The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development. These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.

No MeSH data available.


Related in: MedlinePlus

Effect on ability of cells to readhere after KP418 and KP1019 treatment. MDA-MB-231, MCF-7, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then the cells were removed from the flasks, collected, resuspended and seeded on 96-well plastic plates previously coated with poly-L-lysine, fibronectin, collagen IV and Matrigel. After 30 and 60 minutes of incubation cells that adhered to the substrates were detected by the SRB test. Data are the percent of variation versus controls calculated from the mean  ±  S.D. of two experiments, each performed in triplicate.  *, P < .05 versus controls, ANOVA, and Tukey-Kramer post test.
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fig3: Effect on ability of cells to readhere after KP418 and KP1019 treatment. MDA-MB-231, MCF-7, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then the cells were removed from the flasks, collected, resuspended and seeded on 96-well plastic plates previously coated with poly-L-lysine, fibronectin, collagen IV and Matrigel. After 30 and 60 minutes of incubation cells that adhered to the substrates were detected by the SRB test. Data are the percent of variation versus controls calculated from the mean ± S.D. of two experiments, each performed in triplicate. *, P < .05 versus controls, ANOVA, and Tukey-Kramer post test.

Mentions: The propensity to readhere to fibronectin (F), collagen IV (C), and Matrigel (M), in comparison to poly-L-lysine (P), of MDA-MB-231, MCF-7, and HBL-100 cells, following 1 hour challenge with 10−4 M KP1019 and KP418 was studied exposing cells to the compounds while they were adherent to the growth substrate (Figure 3). The two metal compounds show no significant modifications of the cell ability to readhere after treatment with the exception of KP1019 that significantly reduces the attachment of MCF-7 to fibronectin.


Inhibitory Effects of the Ruthenium Complex KP1019 in Models of Mammary Cancer Cell Migration and Invasion.

Bergamo A, Masi A, Jakupec MA, Keppler BK, Sava G - Met Based Drugs (2009)

Effect on ability of cells to readhere after KP418 and KP1019 treatment. MDA-MB-231, MCF-7, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then the cells were removed from the flasks, collected, resuspended and seeded on 96-well plastic plates previously coated with poly-L-lysine, fibronectin, collagen IV and Matrigel. After 30 and 60 minutes of incubation cells that adhered to the substrates were detected by the SRB test. Data are the percent of variation versus controls calculated from the mean  ±  S.D. of two experiments, each performed in triplicate.  *, P < .05 versus controls, ANOVA, and Tukey-Kramer post test.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2748298&req=5

fig3: Effect on ability of cells to readhere after KP418 and KP1019 treatment. MDA-MB-231, MCF-7, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then the cells were removed from the flasks, collected, resuspended and seeded on 96-well plastic plates previously coated with poly-L-lysine, fibronectin, collagen IV and Matrigel. After 30 and 60 minutes of incubation cells that adhered to the substrates were detected by the SRB test. Data are the percent of variation versus controls calculated from the mean ± S.D. of two experiments, each performed in triplicate. *, P < .05 versus controls, ANOVA, and Tukey-Kramer post test.
Mentions: The propensity to readhere to fibronectin (F), collagen IV (C), and Matrigel (M), in comparison to poly-L-lysine (P), of MDA-MB-231, MCF-7, and HBL-100 cells, following 1 hour challenge with 10−4 M KP1019 and KP418 was studied exposing cells to the compounds while they were adherent to the growth substrate (Figure 3). The two metal compounds show no significant modifications of the cell ability to readhere after treatment with the exception of KP1019 that significantly reduces the attachment of MCF-7 to fibronectin.

Bottom Line: The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects.The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development.These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.

View Article: PubMed Central - PubMed

Affiliation: Callerio Foundation Onlus, Via A. Fleming 22-31, 34127 Trieste, Italy.

ABSTRACT
The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects. The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development. These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.

No MeSH data available.


Related in: MedlinePlus