TMJ-105, an extract of Carpesium cernuum, induced G2/M phase arrest and apoptosis via the JAK2/STAT3 axis and MAPKs signaling pathway in leukemia HEL cells

Leukemia is a malignant tumor of the hematologic system. Studies have shown that cernuumolide J (TMJ-105), an extract of Carpesium cernuum, has anti-cancer effects, but the underlying mechanism is unclear. In this study, we investigated the effect of TMJ-105 on the proliferation of human leukemia HEL cells and its molecular mechanism. MTT analysis showed TMJ-105 had revealed that it shows significant IC₅₀ in HEL cells at lower doses (1.79 ± 0.29 μmol/L) than in K562 cells (3.89 ± 0.80 μmol/L), and the suppression of HEL cell proliferation was time- and concentration-dependent. Meanwhile, TMJ-105 induced G2/M phase blockage, leading to DNA damage in HEL cells. TMJ-105 promoted HEL cells to release of Reactive Oxygen Species (ROS) and changed mitochondrial membrane potential (MMP). Furthermore, TMJ-105 induced Apoptosis by upregulating the cleaved-caspase9 and cleaved-caspase3 protein expression, while Caspase pan inhibitor (Z-VAD-FMK) blocked the inhibition effect. Finally, TMJ-105 downregulated the phosphorylation of JAK2, STAT3 and ERK, and activated the phosphorylation of JNK and p38. Collectively, these results demonstrated that TMJ-105 inhibited proliferation of leukemia cells and the underlying mechanism via the JAK2/STAT3 axis and MAPKs signaling pathway. Based on these results, the present study suggested the sesquiterpene lactone TMJ-105 is a new chemotherapeutic agent for the treatment of leukemia.

Apoptosis; Carpesium cernuum; JAK2/STAT3; Leukemia; MAPKs; TMJ-105.