Alantolactone inhibits T-cell lymphoma progression by suppressing CD47 expression via the PI3K/AKT and ERK signaling pathways

T-cell lymphoma (TCL) is a malignant tumor caused by abnormal proliferation of T cells, and its specific pathogenesis remains unclear. Currently, there is still a lack of highly effective therapeutic drugs in clinic. As a semi-terpene lactone compound, alantolactone (ATL) is mainly used to treat diseases such as asthma, and its role in TCL has not been revealed. This study demonstrated that ATL not only significantly inhibits the proliferation and migration of TCL cells and induces apoptosis in vitro, but also exhibits significant anti-tumor effects in tumor-bearing mice. Meanwhile, ATL can markedly enhance the sensitivity of TCL cells to chemotherapeutic drugs such as decitabine. Mechanistically, multi-omics analysis confirmed that ATL restricts TCL progression by negatively regulating the PI3K/AKT and ERK signaling pathway. Furthermore, our study also found that ATL-mediated suppression of these pathways leads to significant downregulation of CD47 expression. In summary, this study is the first to elucidate that ATL exhibits significant anti-TCL effects both in vitro and in vivo, suggesting its potential as a novel clinical strategy for the treatment of TCL.