Abstract In a recent study we could show that neopterin inhibits nitric oxide-induced apoptosis in ovarian carcinoma cells. This may provide an explanation for the correlation between increased levels of neopterin derivatives and the unfavorable prognosis in patients with ovarian cancer that has been described in the literature. To obtain additional information on the mode of action of neopterin derivatives within the tumor environment, we studied the effects of neopterin (100 and 1000 μΜ) and 7,8-dihydroneopterin (100, 500, and 1000 μΜ) on mitochondrial dehydrogenase activity in three different ovarian carcinoma cell lines (2774, HOC-1, and OVCAR-3). 7,8-dihydroneopterin was an effective stimulus of mitochondrial enzyme turnover rate in any cell culture model under investigation. This suggests that the pteridine compound stabilizes tumor cell viability and therefore acts as a promotor of tumor growth. In contrast to 7.8-dihydroneopterin, neopterin did not affect mitochondrial dehydrogenases in 2774, HOC-7, or OVCAR-3 cells. However, in HOC-7 and OCVAR-3, neopterin was found to antagonize the stimulating effects of 7,8-dihydroneopterin. This might be due to the different impact of both pteridine compounds on the redox status in these cells. Our new data provide further evidence of distinct biochemical effects of neopterin derivatives in ovarian carcinoma cells. Neopterin and 7,8-dihydroneopterin may be involved in separate stages of cellular changes that lead to malignancy or promote tumor progression.
Biological effects of ultrasound exposure on adriamycin-resistant and cisplatin-resistant human ovarian carcinoma cell lines in vitro
