Chamaejasmine Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells through a Ros-Mediated Mitochondrial Pathway

Molecules

Hongyang Yu¹  Tingting Zhang¹  Li Cai¹  Yuanyuan Qu¹  Songliu Hu¹  Guanglu Dong¹  Rongwei Guan¹  Xiangying Xu¹ 

[1] ¹Department of Radiation Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China

关键词: chamaejasmine;    A549;    Apoptosis;    ROS;    mitochondrial;   

DOI  :  10.3390/molecules16108165

来源: mdpi

【 摘 要 】

In the present study, the anticancer activity of chamaejasmine towards A549 human lung adenocarcinoma cells was investigated. In order to explore the underlying mechanism of cell growth inhibition of chamaejasmine, cell cycle distribution, ROS generation, mitochondrial membrane potential (Δψ_m) disruption, and expression of cytochrome c, Bax, Bcl-2, caspase-3, caspase-9 and PARP were measured in A549 cells. Chamaejasmine inhibited the growth of A549 cells in a time and dose-dependent manner. The IC₅₀ value was 7.72 µM after 72 h treatment. Chamaejasmine arrested the cell cycle in the G2/M phase and induced apoptosis via a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that chamaejasmine inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage. All of these signal transduction pathways are involved in initiating apoptosis. To the best of our knowledge, this is the first report demonstrating the cytotoxic activity of chamaejasmine towards A549 in vitro.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.