Project description: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 (CM)-stimulated CL1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL1-5-bearing severe combined immunodeficiency mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I had no significant cytotoxicity. Real-time quantitative polymerase chain reaction (RTQ-PCR), luciferase reporter assay, and an electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8 (IL-8), the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor kappaB in CM-stimulated CL1-5 cells. Microarray and pathway analysis of tumor-related genes identified the differentially expressed genes responding to tanshinone I, and these results were validated by RTQ-PCR. The responsive genes included human platelet-derived growth factor beta chain, Shb, H-ras, N-Ras, mitogen-activated protein kinase kinase 3, phosphoinositide-3-kinase, CD44, Rac1, and collagen type IV; these genes may be associated with the Ras MAPK 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 IL-8, Ras MAPK, and Rac1 signaling pathways. Keywords: treatment with dose respone, cDNA array
Project description:Phenotypically, we observed that both genistein and Tanshinone I exert the inhibitory effects on the proliferation and metastasis of cervical cancer. The aim of this study was to comprehensively decipher the anti-metastasis effect and molecular mechanism of genistein and Tanshinone I on the cervical cancer. The results showed that genistein and Tanshinone I strongly change the RNA profiling of the cervical cancer cells in different manners: genistein mainly targets on regulation of RNA transcription, central carbon metabolism in cancer, microRNAs in cancer and focal adhesion etc; Tanshinone I mainly effects on central carbon metabolism in cancer, mitophagy process.