112 / 2021-10-24 11:35:18

Ageladine A inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, ferroptosis, and ferroptosis

Ageladine A,NSCLC,cell cycle arrest,ferroptosis

Non-small cell lung cancer (NSCLC) is one of the leading cancer-related causes of morbidity and mortality worldwide. Despite advances in lung cancer therapy, there is an urgent need to discover novel therapeutic agents for NSCLC. Ageladine A is a natural compound isolated from the sponge of Agelasnakamurai in 2003. Ageladine A belongs to a bromopyrrole alkaloid, which has a unique structure and good biological activity. We have well synthesized this natural product. Our experiments demonstrate that Ageladine A has the ability to induce multiple modes of mixed cell death and may have multiple targets. Ageladine A strongly induces lipid peroxidation with depletion of SLC7A11-GPX4 axis and ferroprotein FTH1 within cancer cells and induces ferroptosis. Similarly, Ageladine A induced elevation of a range of autophagy parameters beclin and LC3, mediating autophagy in cancer cells. Fer-1, an ferroptosis inhibitor, and wort, an autophagy inhibitor, could partially rescue Ageladine A-induced cell death. Meanwhile, Ageladine A induced cycle arrest and prevented cell migration, with the depletion of related genes. In conclusion, we believe that Ageladine A has a good anticancer effect and has clinical value.