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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

Chemical structures of NAMI-A, KP1019, and KP418.
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Related In: Results  -  Collection


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fig1: Chemical structures of NAMI-A, KP1019, and KP418.

Mentions: The aim of this study is to evaluate the effects of KP1019, in comparison to its bis-imidazole analogue KP418 (Figure 1), in an in vitro model of tumour invasion and metastasis. Although isostructural with KP1019, KP418 showed a slower reduction rate [4], but higher toxicity in therapeutically active doses in vivo in a model of chemically induced autochthonous colorectal cancer [5] and very low cytotoxicity in human cancer cell lines [6]. Effects of KP1019 (but not KP418) on adhesion properties of cancer cells were first suggested by the simple observation that human SW480 colon carcinoma cells resist harvesting by trypsinisation upon treatment with KP1019 in concentrations in the 10−4 M range for as short as 30 minutes [6]. Microscopic examination revealed structures tentatively considered as stress fibres (B. Marian, personal communication). Although not examined in detail, these observations were reminiscent of the strong actin-dependent adhesion of tumour cells induced by short-term exposure to the investigational antimetastatic ruthenium-based drug NAMI-A [7], raising the question whether KP1019 is capable of affecting cellular properties related to the processes of tumour invasion and metastasis.


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)

Chemical structures of NAMI-A, KP1019, and KP418.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Chemical structures of NAMI-A, KP1019, and KP418.
Mentions: The aim of this study is to evaluate the effects of KP1019, in comparison to its bis-imidazole analogue KP418 (Figure 1), in an in vitro model of tumour invasion and metastasis. Although isostructural with KP1019, KP418 showed a slower reduction rate [4], but higher toxicity in therapeutically active doses in vivo in a model of chemically induced autochthonous colorectal cancer [5] and very low cytotoxicity in human cancer cell lines [6]. Effects of KP1019 (but not KP418) on adhesion properties of cancer cells were first suggested by the simple observation that human SW480 colon carcinoma cells resist harvesting by trypsinisation upon treatment with KP1019 in concentrations in the 10−4 M range for as short as 30 minutes [6]. Microscopic examination revealed structures tentatively considered as stress fibres (B. Marian, personal communication). Although not examined in detail, these observations were reminiscent of the strong actin-dependent adhesion of tumour cells induced by short-term exposure to the investigational antimetastatic ruthenium-based drug NAMI-A [7], raising the question whether KP1019 is capable of affecting cellular properties related to the processes of tumour invasion and metastasis.

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