The Polyamine Analogues PG11144 and PG11047 Inhibit Cell Proliferation and Decrease the Malignancy in LNCap-FGC Prostate Cancer Cells in Normoxia and Hypoxia

Sammanfattning: Abstract One of many new targets when looking for anti-cancer treatment is the polyamine pathway, which is essential in cell proliferation, gene regulation and cell death. A way to intervene with this pathway is to use compounds called polyamine analogues. Depletion in the intracellular polyamine pools results in decrease in cell proliferation, something that is desirable in cancer treatment. In this study the effect of two different polyamine analogues, PG11144 and PG11047 (10 µM concentration), on the prostate cancer cell line LNCap-FGC was investigated in both normoxia (21% O2) and hypoxia (1% O2) to better mimic the actual conditions in the tumor. Tumors often contain oxygen-deprived areas, which have been reported to be involved in the development of malignancy. When the cells were cultured in hypoxia, the colony forming efficiency in soft agar increased 100-fold compared to culturing in normoxia, indicating an increase in malignancy. PG11144 or PG11047 treatment decreased the colony formation efficiency of cells grown in hypoxia. The expression of β-catenin, a marker of malignancy, decreased in PG11144- or PG11047-treated cells grown in normoxia and hypoxia, with PG11144 being the most effective. Treatment with either compound reduced cell proliferation, especially in normoxia. Altogether, the data show promising anticancer activities of both compounds in LNCap-FGC cells grown in normoxia and hypoxia.