Abstract:
Cancer is one of the most important problems of modern societies. Recently, studies have
reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator
receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this
study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and
their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase
(LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast
(BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were
mainly increased in the micromolar concentrations of the studied compounds in both cell lines.
Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM
(ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except
PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our
results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells
exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and
PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ
modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer
properties evidenced by their action at high concentrations and non-selective effects against BJ and
A549 cells.
Keywords: 4-t
