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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 of KP418 and KP1019 on MMPs production and/or activity. MDA-MB-231, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then incubated for additional 24 hours in serum-starved complete medium containing 0.1% BSA. Supernatants containing MMPs were collected and concentrated and equal protein amounts (100 μg) subjected to SDS-PAGE. Gelatine digestion by proteases is detected as white bands against a blue background (a, b). Band digestion is quantified by using Image Master 2D version 4.01 and Magic Scan 32 version 4.3 software (c).
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fig6: Effect of KP418 and KP1019 on MMPs production and/or activity. MDA-MB-231, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then incubated for additional 24 hours in serum-starved complete medium containing 0.1% BSA. Supernatants containing MMPs were collected and concentrated and equal protein amounts (100 μg) subjected to SDS-PAGE. Gelatine digestion by proteases is detected as white bands against a blue background (a, b). Band digestion is quantified by using Image Master 2D version 4.01 and Magic Scan 32 version 4.3 software (c).

Mentions: The effects of the two metal compounds on the matrix metallo proteinases (MMP-2 and MMP-9) production and/or activity were studied with the gelatine zymography test. MDA-MB-231 cells produce the 92 KDa MMP-9 in appreciable amounts whereas HBL-100 cells prevalently produce the 72 KDa MMP-2. KP1019 reduced the production/activity of both MMP-2 and MMP-9 by approximately 65–75% of controls, whereas KP418 reduced MMP-9 activity by about 40% of controls (Figure 6).


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 of KP418 and KP1019 on MMPs production and/or activity. MDA-MB-231, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then incubated for additional 24 hours in serum-starved complete medium containing 0.1% BSA. Supernatants containing MMPs were collected and concentrated and equal protein amounts (100 μg) subjected to SDS-PAGE. Gelatine digestion by proteases is detected as white bands against a blue background (a, b). Band digestion is quantified by using Image Master 2D version 4.01 and Magic Scan 32 version 4.3 software (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: Effect of KP418 and KP1019 on MMPs production and/or activity. MDA-MB-231, and HBL-100 cells were treated for 1 hour with KP418 and KP1019 10−4 M, then incubated for additional 24 hours in serum-starved complete medium containing 0.1% BSA. Supernatants containing MMPs were collected and concentrated and equal protein amounts (100 μg) subjected to SDS-PAGE. Gelatine digestion by proteases is detected as white bands against a blue background (a, b). Band digestion is quantified by using Image Master 2D version 4.01 and Magic Scan 32 version 4.3 software (c).
Mentions: The effects of the two metal compounds on the matrix metallo proteinases (MMP-2 and MMP-9) production and/or activity were studied with the gelatine zymography test. MDA-MB-231 cells produce the 92 KDa MMP-9 in appreciable amounts whereas HBL-100 cells prevalently produce the 72 KDa MMP-2. KP1019 reduced the production/activity of both MMP-2 and MMP-9 by approximately 65–75% of controls, whereas KP418 reduced MMP-9 activity by about 40% of controls (Figure 6).

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