Artemisinin alleviates cisplatin-induced damage in GC-1 spermatogonia through ER stress mechanisms

Artemisinin, a compound derived from <i>Artemisia annua</i>, is primarily utilized for malaria treatment. Its mechanism of action involves the rapid and effective inhibition of protein synthesis in malarial parasites. Recently, artemisinin has garnered extensive research attention for its anticancer, antioxidant, and anti-inflammatory properties, as well as its potential role as an adjuvant in cancer treatment. Cisplatin is a commonly used anticancer agent; however, its therapeutic benefits are accompanied by side effects that negatively impact male reproductive function. In this study, the mechanism of the protective effect of artemisinin against cisplatin-induced cytotoxicity was investigated. Type B mouse spermatogonia (GC-1 spg cells), derived from mouse testes, were treated with various concentrations of artemisinin (10-200 μM) to identify the optimal concentration for promoting cell proliferation. Cisplatin induced antiproliferative effects and apoptotic cell death in GC-1 spg cells, whereas the combination of cisplatin and artemisinin restored cell proliferation and reduced apoptosis. Treatment with cisplatin resulted in elevated levels of endoplasmic reticulum (ER) stress-related factors, such as Bip/GRP78, PDI, and Ero1-la, in GC-1 spg cells, while the combination with artemisinin effectively inhibited and reduced these levels. Additionally, cisplatin increased inflammatory markers, including COX2, iNOS, and NF-κB, which were subsequently decreased by artemisinin. This study evaluates artemisinin, a naturally derived compound, as a potential mitigator of side effects on male germ cells during cisplatin-based anticancer treatment. In conclusion, these findings suggest that artemisinin may serve as a supplement or functional agent in cancer therapy.