Cytostatic effects of increased lipoperoxide levels on malignant cells is dependent by ros-mediated modulation of angiogenesis and proliferation markers

Exposure to LOOHs shows to inhibit growth activity in 5637 and HECV cells. • In HECV exposed to CM from untreated 5637, prolifer ation rate resulted marked increased; exposure to CM derived from LOOH-treated 5637 (CM LOOH) evidenced a significant reduction of HECV proliferation. • Underlying the growth inhibitory effect of LOOHs on 5637 cells, APRIL protein expression evidenced a dose dependent decrease until 72 h. • ° and TBARs levels, During LOOH treatments, 5637 and HECV evidenced an increase of both O as indexes of oxidative stress, in a time dependent way. 2 • In HECV exposed to CM LOOH, iNOS gene expression resulted decreased with time/dose dependent way. • 5637 culture during LOOH treatments showed a significant reduction of VEGF and Hsp70 mRNA expressions. • In HECV CM LOOH, Hsp70 gene expression decreased significantly. • During exposure to LOOHs, 5637, HECV and HECV CM LOOH evidenced a time-dose constant increase cleavage of PARP. These preliminary data suggest that LOOH exposure may exhibit different effects on cancer and normal cell proliferation. In our experimental model, LOOH growth inhibitory activity seems to be related to reduction of proliferation and angiogenic markers, such as APRIL, iNOS, Hsp70 and VEGF .