Cytotoxicity of arctigenin and matairesinol against the T-cell lymphoma cell line CCRF-CEM.
OBJECTIVE
Arctigenin and matairesinol possess a diversity of bioactivities. Here we investigated the cytotoxicity of arctigenin and matairesinol against a T-cell lymphoma cell line CCRF-CEM and the underlying mechanisms that have not been explored before.


METHODS
The cytotoxic activity was investigated using MTT assay. The cell cycle arrest and reactive oxygen species (ROS) accumulation were determined by flow cytometric analysis. The apoptosis induction was assessed using Annexin V/Propidium Iodide assay. The gene quantification analysis was measured through real-time polymerase chain reaction.


RESULTS
Arctigenin and matairesinol exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 μm and 4.27 ± 0.41 μm, respectively. In addition, both lignans arrest CCRF-CEM cells in the S phase. Furthermore, they could induce apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Interestingly, the lignans differentially regulated the expression of several key genes involved in apoptosis pathways, including Bax, Bad and caspase-9. Moreover, both lignans could increase ROS levels in CCRF-CEM cells.


CONCLUSIONS
Our study provides an insight into the potential of arctigenin and matairesinol as good candidates for the development of novel agents against T-cell lymphoma.
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Shan
S
Su
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Xinlai
X
Cheng
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Michael
M
Wink
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C068935:matairesinol; D053453:Caspase 9; C071942:arctigenin
T-cell lymphoma; apoptosis; arctigenin; matairesinol