Background:
Hydantoin and its newly synthesized derivatives have recently become a focus of interest
due to their numerous biological activities and newly emerging beneficial effects in different pathological
conditions, including cancer.
Objective:
The aim of this study was to evaluate the possible anti-tumor mechanisms of a series of newly synthesized
3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in different aspects of cell physiology
of human colon cancer cell line, HCT-116.
Methods:
The increasing concentrations of derivatives (0.01µM up to 100µM) were applied to cells during 24h,
48h, and 72h after which the evaluation of proliferation, apoptosis, oxidative/anti-oxidative status, nitrite production,
and migration/invasion potential of treated cells was performed.
Results:
All tested compounds expressed the dose- and time-dependent anti-proliferative and pro-apoptotic
activities against HCT-116 cells. The investigated derivatives induced a decrease in levels of oxidative stress
parameters and an increase in levels of nitrite production by treated cells suggesting their significant antioxidative
effects. The cell migration index and expression level of tumor invasion-promoting metalloproteinase-
9 (MMP-9) gene were significantly decreased after treatment with the tested hydantoin derivatives implicating
their inhibitory role in colon cancer cell motility and invasion processes. The mRNA level of cyclooxygenase-2
(COX-2) gene as a pro-inflammatory gene related to colorectal carcinogenesis was reduced compared to values
in the non-treated control cells indicating the significant anti-inflammatory/anti-tumor effects of these compounds.
Conclusion:
The obtained results show the significant anti-tumor potential of tested derivatives, especially 3-
benzyl-5-isopropyl-5-phenylhydantoin and 3-(4-chlorobenzyl)-5-isopropyl-5-phenylhydantoin, suggesting their
potential usage in the development of more effective chemotherapies.