In vitro proliferation of fibrosarcoma cells depends on intact functions of lipoxygenases and cytochrome P-450-monooxygenase

Časopis: CANCER INVESTIGATION 22, 234-247
Autoři: Hoferova, Z., Soucek, K., Hofmanova, J., Hofer, M., Chramostova, K., Fedorocko, P., Kozubik, A.
Rok: 2004


Proliferation of mouse fibrosarcoma cells G:5:113 was studied in vitro after affecting particular pathways of arachidonic acid metabolism by selected inhibitors. After 48 hours of cultivation with nonspecific lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin; a specific 12-lipoxygenase inhibitor, baicalein; and inhibitor of five-lipoxygenase activating protein, MK-886, markedly suppressed the number of cells and induced significant changes in cell cycle distribution in a dose-dependent manner. While proadifen, an inhibitor of cytochrome P-450-monooxygenase, applied in low concentrations, increased the cell number, at higher concentrations, it inhibited cell proliferation and significantly changed the cell cycle. Cyclooxygenase inhibitors, ibuprofen, flurbiprofen, and diclofenac suppressed cell numbers only moderately without any changes in the cell cycle. The occurrence of apoptosis was not significant for any of the selected drugs in comparison with untreated control cells. Moreover, not even one of the drugs caused the specific cleavage of poly (ADP-ribose) polymerase to the 89-kDa fragment, however, a decrease in total amount of this protein was observed after treatment with NDGA and esculetin. We conclude that the proliferation ability of fibrosarcoma cells G:5:113 in vitro depends on intact functions of 5-lipoxygenase, 12-lipoxygenase, and cytochrome P-450-monooxygenases, and that the effects of inhibitors do not include regulation of apoptosis.