Anticancer effects of tanshinone I in human non-small cell lung cancer

Abstract

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-KB in conditioned medium-stimulated CL1-5 cells. Microarray and pathway analysis of tumorrelated 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.

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…In the DU145 human prostate cancer cell line, tanshinone I induces apoptosis of cancer cells by activating the mitochondrial pathway (57). In a paper published in 2008, Tanshinone I was reported to suppress proliferation of NSCLC cells through the NF-κB pathway (58). These benzoquinones target several pathways: i) mitochondrial pathway; ii) NF-κB pathway; iii) PI3K/ Akt pathway; iv) ERK1/2 pathway; and v) cell cycle pathway.…”

Tanshinone I induces human colorectal cancer cell apoptosis: The potential roles of Aurora A-p53 and survivin-mediated signaling pathways

“…Since T1 exhibited inhibitory effects on breast and lung cancer (27)(28)(29), we sought to treat human colorectal cancer cell lines as well as normal colon epithelial cells with T1. After 72 h of T1 treatment at various concentrations, HCT116 colorectal cell with wild-type p53 protein displayed decreased viability in a dose-dependent manner.…”

AP-1 Transcription Factor Serves as a Molecular Switch between Chlamydia pneumoniae Replication and Persistence

“…We used tanshinone IIA, an isolate of the root of Salvia miltiorrhiza Bunge, which was shown to specifically inhibit the c-Jun/c-Fos AP-1 complex, preventing DNA binding and the subsequent transcriptional activity (31,38). Blocking AP-1 DNA binding, using tanshinone IIA, resulted in a drastic change in infectivity and chlamydial development.…”