**Background**
Cancer cells often exhibit altered redox homeostasis to survive under high levels of oxidative stress, which is a hallmark of malignancy. Sulfiredoxin (Srx) plays a critical role in this process by reducing overoxidized peroxiredoxins back to their active state, thereby protecting cells from lethal reactive oxygen species (ROS) accumulation. Because cancer cells are more dependent on these antioxidant mechanisms than normal cells, targeting sulfiredoxin presents a promising strategy for inducing selective cytotoxicity. By inhibiting the repair of peroxiredoxins, it is possible to trigger mitochondrial damage and apoptosis in malignant tissues. In this context, we will introduce a potent sulfiredoxin inhibitor – J14.
**Definition**
J14 is a reversible sulfiredoxin inhibitor with an IC50 value of 8.1 μM.
**In Vitro and In Vivo Studies**
The J14 description highlights its ability to induce intracellular ROS accumulation and subsequent cancer cell death. According to J14 in vitro data, treatment with J14 (0-100 μM; 0-96 hours) inhibited the growth of A549 cells in both a concentration- and time-dependent manner, with a half inhibitory concentration (IC50) for growth of 15.7 μM. Further investigation revealed that J14 (20 μM; 48-72 hours) triggered the release of cytochrome c into the cytosol and activated caspase-3 and caspase-9, indicating that J14 induces oxidative mitochondrial damage and caspase-mediated apoptosis. Additionally, J14 treatment significantly increased the accumulation of sulfinic peroxiredoxins and intracellular ROS, resulting in approximately 40% cell death in A549 cells within 96 hours.
Regarding J14 in vivo efficacy, studies using six-week-old BALB/c nude female mice injected with A549 cells demonstrated significant antitumor activity. J14 (50 mg/kg; intraperitoneal injection; daily for 16 days) significantly reduced the average tumor volume, as well as the mass and weight of excised primary tumors, compared to control groups, without exhibiting acute toxicity. In conclusion, J14 is a reversible sulfiredoxin inhibitor that promotes the preferential death of cancer cells through ROS-mediated mitochondrial damage.
Keywords
J14, 1043854-13-2, J 14, J-14, Reactive Oxygen Species (ROS), Sulfiredoxin, cytotoxicity, mitochondrial, damage, cancer, death, lung, adenocarcinoma, cells, Inhibitor
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