Ferritinophagy-Mediated Ferroptosis and Activation of Keap1/Nrf2/HO-1 Pathway Were Conducive to EMT Inhibition of Gastric Cancer Cells in Action of 2,2'-Di-pyridineketone Hydrazone Dithiocarbamate Butyric Acid Ester.

In metastasis of cancer cells, the epithelial-mesenchymal transition (EMT) is prerequired. Ferroptosis is an iron-mediated cellular death process, but whether it involves EMT regulation remains elusive. In addition, how stress responders (Nrf2) respond to the redox alteration and cross-talking between them needs to be determined.

Ferritinophagy-Mediated ROS Production Contributed to Proliferation Inhibition, Apoptosis, and Ferroptosis Induction in Action of Mechanism of 2-Pyridylhydrazone Dithiocarbamate Acetate.

Reactive oxygen species (ROS) production is involved in the mechanism of action of a number of drugs, but the biological effects of ROS remain to be clarified. Furthermore, ferroptosis involves iron-dependent ROS production that may be derived from ferritinophagy; however, the association between ferroptosis and ferritinophagy has not been fully established. The present study demonstrated that dithiocarbamate derivatives (iron chelators) exhibited antineoplastic properties involving ferritinophagy induction, but whether the underlying mechanisms involved ferroptosis was unknown.

The DpdtbA induced EMT inhibition in gastric cancer cell lines was through ferritinophagy-mediated activation of p53 and PHD2/hif-1α pathway.

Previous studies have shown that epithelial-mesenchymal transition (EMT) involves reactive oxygen species (ROS) production, but how ferritinophagy-mediated ROS production affects EMT status remains obscure. 2,2'-di-pyridylketone hydrazone dithiocarbamate s-butyric acid (DpdtbA), an iron chelator, exhibited interesting antitumor activities against gastric and esophageal cancer cells. As an extension of our previous research, in this paper we presented the effect of DpdtbA on EMT regulation of gastric cancer lines (SGC-7901 and MGC-803) in both normoxic and hypoxic conditions.