[Effect of danshensu on redox state and relevant nuclear transcription factors in non-small cell lung cancer A549 cells].
OBJECTIVE
To study the molecular mechanism of anti-tumor effect of Danshensu (DSS) focusing on whether it is related to its antioxidation effect on redox state of non-small cell lung cancer A549 cells and relevant nuclear transcription factors and signal pathway.


METHODS
DPPH radical scavenging, ferric reducing, ferrous iron chelating assay and DCFH-DA fluorescence staining of ROS were introduced to detect antioxidant activity and ROS scavenging activity in vitro; MTf was adopted to analyze the effect of DSS on A549 cells viability at different time and dose. Western blot was used to detect the effect of DSS on the protein expression of hypoxiainducible factor HIF-1alpha and redox regulating transcription factor Nrf2 in A549 cells and the phosphorylation of upstream Akt, ERK1/2 MAPK.


RESULTS
DSS could reduce the ROS level in A549 cells in a dose-dependent manner, which was related to it's strong DPPH radical scavenging activity. Moreover, DSS inhibited A549 cells proliferation in both dose- and time- dependent manner. Further study on molecular mechanism indicated that DSS suppressed redox regulator Nrf2, and down-regulated the phosphorylation of Akt and ERK1/2. However, DSS had no effect on HIF-la expression.


CONCLUSIONS
DSS might have the effect on treating non-small cell lung cancer by scavenging ROS and then inhibiting phosphorylation of Akt, ERK1/2 and down-regulating Nrf2 expression in A549 cells.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. tl20082008@126.com
Li
L
Tao
Sheng
S
Wang
Yang
Y
Zhao
Wenxing
W
Chen
Aiyun
A
Wang
Yin
Y
Lu
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3