Anticancer effects of tanshinone I in human non-small cell lung cancer.
Tanshinones are the major bioactive compounds of Salvia miltiorrhiza Bunge (Danshen) roots, which are used in many therapeutic remedies in Chinese traditional medicine. We investigated the anticancer effects of tanshinones on the highly invasive human lung adenocarcinoma cell line, CL1-5. Tanshinone I significantly inhibited migration, invasion, and gelatinase activity in macrophage-conditioned medium-stimulated CL1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL1-5-bearing severe combined immunodeficient mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I did not have direct cytotoxicity. Real-time quantitative PCR, luciferase reporter assay, and electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8, the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor-kappaB in conditioned medium-stimulated CL1-5 cells. Microarray and pathway analysis of tumor-related genes identified the differentially expressed genes responding to tanshinone I, which may be associated with the Ras-mitogen-activated protein kinase and Rac1 signaling pathways. These results suggest that tanshinone I exhibits anticancer effects both in vitro and in vivo and that these effects are mediated at least partly through the interleukin-8, Ras-mitogen-activated protein kinase, and Rac1 signaling pathways. Although tanshinone I has a remarkable anticancer action, its potential anticoagulant effect should be noted and evaluated.
Lee
Chen-Yu
CY
Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, Taichung, Taiwan 40227, Republic of China.
Sher
Hui-Fang
HF
Chen
Huei-Wen
HW
Liu
Chun-Chi
CC
Chen
Ching-Hsien
CH
Lin
Choun-Sea
CS
Yang
Pan-Chyr
PC
Tsay
Hsin-Sheng
HS
Chen
Jeremy J W
JJ
D045784:Abietanes; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D016209:Interleukin-8; D010616:Phenanthrenes; D012333:RNA, Messenger; C021751:tanshinone