The objective of the present study was to determine the in-vitro effect of
Abietyl-Isothiocyanate (
ABITC), a representative of a new class of anti-
cancer drugs, on
endometrial cancer (EC) cell lines.
ABITC at concentrations ≥1 μM displayed dose-dependent and selective cytotoxicity to EC cell lines (ECC-1, AN3CA, RL95-2) in comparison to other
cancer cell lines.
After treatment with
ABITC, ECC-1 unlike control cells displayed hallmark features of apoptosis including
chromatin condensation and nuclear fragmentation. At concentrations below the IC50,
ABITC exerted anti-proliferative effects by blocking cell-cycle progression through G0/G1 and S-phase. In addition, cells attempted to counteract
drug treatment by pro-survival signaling such as deactivation of JNK/SAPK and
p38 MAPK and activation of AKT and ErK1/2.
ABITC also altered
EGF-receptor phosphorylation. At a concentration of 5 μM
ABITC generated an excess amount of
reactive oxygen species (ROS) and displayed pro-apoptotic signaling such as activation of
caspase-8, JNK-SAPK and deactivation of PARP-1. Co-treatment with an
antioxidant blocked the
drug effects by reducing ROS generation, cytotoxicity and pro-apoptotic signaling. In summary, novel
isothiocyanate ABITC is an anti-proliferative and selectively cytotoxic
drug to EC cells in-vitro. Key mechanisms during cell death are predominantly correlated to excess generation of ROS. We suggest the further development of
ABITC as a potential therapeutic by studying the
drug efficacy in EC in-vivo models.