题目: Oxalicumone A,a new dihydrothiophene-condensed sulfurchromone induces apoptosis in leukemiacells through endoplasmic reticulum stress pathway

作者: Jie Wang,Qiao-Li Wang,Xu-Hua Nong,Xiao-Yong Zhang,Xin-Ya Xu,Shu-Hua Qi*,Yi-Fei Wang

刊物: European Journal of Pharmacology

刊号: 2016,783:47-55

摘要: Oxalicumone A(POA1), a novel dihydrothiophene-condensed sulfur chromone isolated from the marine fungus Penicillium oxalicum SCSGAF0023, showed cytotoxicity against several cancer cells previously. In this study, its anti-cancer activity and underlying mechanism of this action were investigated in leukemia cells like KG-1a, HL60, U937, and K562. The results showed that POA1 inhibited dose-/time-dependently cell growth and induced apoptosis in leukemia cells. Also, POA1 caused cleavages of caspase-3,8,9 and  PARP1, loss of mitochondrial membrane potential, up-regulations of phosphorylated p38 and JNK, and activation of endoplasmic reticulum stress (ER stress). Furthermore, 4-PBA (an ER stress inhibitor) but not  SP600125 and SB203580 (JNK and p38 inhibitor, respectively) could largely inhibit POA1-induced growth suppression. Additionally, 4-PBA obstructed mitochondrial depolarization and cleavage of PARP1. These data suggested that ER stress pathway might be an important mediator in POA1-induced apop-tosis.  In conclusion, POA1 may have antitumor effects in leukemia cells through the induction of ER stress pathway.