Halofuginone exerts broad-spectrum cytotoxic effects by regulating p-eIF2a-S100A8/A9-calcium signaling, inhibiting global protein synthesis, and reversing the resistance of idarubicin in acute myeloid leukemia [RNA-Seq]

Alkaloid febrifugine., an herbal medicine in China, is prescribed routinely for malaria treatment. Halofuginone (HF), a natural product isolated from alkaloid febrifugine, exhibits anti-tumor and anti-inflammatory ability. Aim of the study: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with low overall survival (OS). Resistance to chemotherapeutic drugs such as idarubicin (IDA) results in treatment failure. This study investigated the role of HF in anti-AML ability and in overcoming IDA resistance in AML cells. Overall design: Ethnopharmacological relevance: Alkaloid febrifugine., an herbal medicine in China, is prescribed routinely for malaria treatment. Halofuginone (HF), a natural product isolated from alkaloid febrifugine, exhibits anti-tumor and anti-inflammatory ability. Aim of the study: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with low overall survival (OS). Resistance to chemotherapeutic drugs such as idarubicin (IDA) results in treatment failure. This study investigated the role of HF in anti-AML ability and in overcoming IDA resistance in AML cells. Materials and methods: Apoptosis, proliferation, cell cycle, and colony were assessed in AML cells treated with HF. RNA sequencing (RNA-seq) was performed to identify the potential targets of HF. Human relapsed and refractory (R/R) AML samples were xenografted into mice to assess the anti-leukemic effects of HF in vivo.