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Pioglitazone, a PPAR-gamma ligand, exerts cytostatic-cytotoxic effects against cancer cells, that do not result from inhibition of proteasome

100%

Mrowka P., Glodkowska E., Mlynarczuk-Bialy I., Bialy L., Kuckelkorn U., Nowis D., Makowski M., Legat M., Golab J.

Acta Biochimica Polonica

2008

tom 55

nr 1

Thiazolidinediones are oral antidiabetic agents that activate peroxisome proliferator-activated receptor-gamma (PPAR-γ) and exert potent antioxidant and anti-inflammatory properties. It has also been shown that PPAR-γ agonists induce G0/G1 arrest and apoptosis of malignant cells. Some of these effects have been suggested to result from inhibition of proteasome activity in target cells. The aim of our studies was to critically evaluate the cytostatic/cytotoxic effects of one of thiazolidinediones (pioglitazone) and its influence on proteasome activity. Pioglitazone exerted dose-dependent cytostatic/cytotoxic effects in MIA PaCa-2 cells. Incubation of tumor cells with pioglitazone resulted in increased levels of p53 and p27 and decreased levels of cyclin D1. Accumulation of polyubiquitinated proteins within cells incubated with pioglitazone suggested dysfunction of proteasome activity. However, we did not observe any influence of pioglitazone on the activity of isolated proteasome and on the proteolytic activity in lysates of pioglitazone-treated MIA PaCa-2 cells. Further, treatment with pioglitazone did not cause an accumulation of fluorescent proteasome substrates in transfected HeLa cells expressing unstable GFP variants. Our results indicate that pioglitazone does not act as a direct or indirect proteasome inhibitor.

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Expression of antitumour response. Role of attachment and cytostatic effect of different substrains of Bacillus Calmette-Guerin to human bladder cancer cells

100%

Janaszek W., Wysokinska T.

Bulletin of the Veterinary Institute in Puławy

1998

tom 42

nr 1

Cytostatic and cytotoxic effects of [E]-2'-deoxy-2'-[fluoromethylene]-cytidine on a solid tumor and a leukemia cell line

80%

Grieb P., Koronkiewicz M., Skierski J. S.

Acta Biochimica Polonica

2000

tom 47

nr 1

(E)-2'-deoxy-2'-(fluoromethylene)-cytidine (FMdC), a deoxycytidine analog displaying a very high toxicity toward a variety of solid tumor cell lines and xenografts, is activated intracellularly by deoxycytidine kinase (dCK). We have compared cytotoxicity of FMdC towards a human promyeolocytic leukemia line HL-60 and a human colorectal carcinoma line COLO-205. Despite dCK activity being by far the highest in cells of lymphoid origin, the effects of FMdC were detectable at the lowest drug concentration only in a solid tumor cell line, and at higher concentrations they were qualitatively similar in the two tumor lines (increased cell protein content, cell cycle block and apoptosis). Apparently, low dCK activity in solid tumor cells sufficiently activates FMdC to yield cytotoxic effects, while high dCK activity in leukemia cells does not increase its cytotoxicity.

Ograniczanie wyników

2 Acta Biochimica Polonica

1 Bulletin of the Veterinary Institute in Puławy

1 Bialy L.

1 Glodkowska E.

1 Golab J.

1 Grieb P.

1 Janaszek W.

1 Koronkiewicz M.

1 Kuckelkorn U.

1 Legat M.

1 Makowski M.

1 Mlynarczuk-Bialy I.

1 Mrowka P.

1 Nowis D.

1 Skierski J. S.

1 Wysokinska T.

1 2008

1 2000

1 1998

Wyniki wyszukiwania

Pioglitazone, a PPAR-gamma ligand, exerts cytostatic-cytotoxic effects against cancer cells, that do not result from inhibition of proteasome

Expression of antitumour response. Role of attachment and cytostatic effect of different substrains of Bacillus Calmette-Guerin to human bladder cancer cells

Cytostatic and cytotoxic effects of [E]-2'-deoxy-2'-[fluoromethylene]-cytidine on a solid tumor and a leukemia cell line