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Direct tumor damage mechanisms of photodynamic therapy

100%

Nowis D., Makowski M., Stoklosa T., Legat M., Issat T., Golab J.

Acta Biochimica Polonica

2005

tom 52

nr 2

Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer treatment regimen. It is a minimally invasive two-stage procedure that requires administration of a photosensitizing agent followed by illumination of the tumor with visible light usually generated by laser sources. A third component of PDT is molecular oxygen which is required for the most effective antitumor effects. In the presence of the latter, light of an appropriate wavelength excites the photosensitizer thereby producing cytotoxic intermediates that damage cellular structures. PDT has been approved in many countries for the treatment of lung, esophageal, bladder, skin and head and neck cancers. The antitumor effects of this treatment result from the combination of direct tumor cell photodamage, destruction of tumor vasculature and activation of an immune response. The mechanisms of the direct photodamage of tumor cells, the signaling pathways that lead to apoptosis or survival of sublethaly damaged cells, and potential novel strategies of improving the antitumor efficacy of PDT are discussed.

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

84%

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.

Ograniczanie wyników

2 Acta Biochimica Polonica

2 Golab J.

2 Legat M.

2 Makowski M.

2 Nowis D.

1 Bialy L.

1 Glodkowska E.

1 Issat T.

1 Kuckelkorn U.

1 Mlynarczuk-Bialy I.

1 Mrowka P.

1 Stoklosa T.

1 2008

1 2005

Wyniki wyszukiwania

Direct tumor damage mechanisms of photodynamic therapy

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