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
Xuenai Wei,
Jingrui Song,
Qing Rao,
Yubing Huang,
Qin Liu,
Jialei Song,
Wei liang,
Shuhui Feng,
Chen Yan,
Yanmei Li
Affiliations
Xuenai Wei
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025, China
Jingrui Song
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China
Qing Rao
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China
Yubing Huang
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China
Qin Liu
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China
Jialei Song
Shool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China
Wei liang
Department of Pharmacy, An Shun City People’s Hospital, Anshun, 561000, Guizhou, China
Shuhui Feng
Beijing Jingmei Group General Hospital, Beijing, 102300, China
Chen Yan
Department of Pharmacy, An Shun City People’s Hospital, Anshun, 561000, Guizhou, China; Corresponding author. Department of Pharmacy, An Shun City People’s Hospital, Anshun 561000, Guizhou, China.
Yanmei Li
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China; Natural Products Research Center of Guizhou Province, Guizhou Province and Chinese Academy of Sciences, Guiyang, 550014, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025, China; Corresponding author. State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou, China.
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.
