Project description:Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. We used microarrays to detail the global programme of gene expression underlying Tan IIA's apoptotic effects on leukemia cells and identified significantly differentially expressed genes (SDEGs). Five human leukemia cell lines were selected for RNA extraction and hybridization on Affymetrix microarrays.To identify genes that are related to Tan IIA sensitivities, we carried out expression profiling on five cell lines.The sample named HL60, MEG01, MOLT,THP1 and U937_control were treated with DMSO. U937 cell line was selected with Tan IIA treatment for 12 h and 24 h, respectively.
Project description:Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. We used microarrays to detail the global programme of gene expression underlying Tan IIA's apoptotic effects on leukemia cells and identified significantly differentially expressed genes (SDEGs).
Project description:Bone marrow mesenchymal stem cells (BMSCs) is a promising cell type for tissue engineering, however, the application of BMSCs are largely hampered for the limited number harvested from bone marrow cells. The methods or strategies that focused on promoting the capacity of BMSCs expansion ex vivo become more and more important. Tanshinone IIA (Tan IIA), the main active components of Danshen, has been found to promote BMSCs proliferation, but the underlying mechanism is still unclear. This present work employed biological techniques combined with quantitative proteome analysis to explore the effect and underlying mechanism of Tan IIA on the ex vivo expansion capacity of BMSCs from human. The results showed that a total of 84 differentially expressed proteins were annotated and among them 51 upregulated proteins and 33 downregulated proteins were identified. Besides, Tan IIA could promote hBMSCs proliferation by regulating the progression of S phase via increasing the release of fibroblast growth factor 2 (FGF2), FGF-mediated PI3K/AKT signaling pathways may play an important role in Tan IIA’s effect on hBMSCs expansion. The results of this study may provide further evidence about the potential of Tan IIA to be used for the research of hBMSCs therapies.
Project description:Gastric cancer is one of the world common causes of cancer death. Many people have suffered, but yet therapeutic methods found. May studies have showedthat Tanshinone IIA, a diterpenequinone, which extracted from the traditional herbal medicine Danshen (Salvia miltiorrhiza),has potential against many kind of cancer types. Our previous studies have demonstrated TIIA can kill gastric cancer AGS cells, but the response signalling is still unclear. Therefore, we used the time-dependent phosphoproteomic approach to reveal the regulatory effects of TIIA in AGS cells. Our results showed that a total of 1092 phosphoprotiens and 3332 phosphopeptides were identified in 3615 phosphorylation sites and 349 phosphosites corresponding to 220 phosphorylated proteins were significantly regulated. Furthermore, by using networkand functionalenrichmentanalyses, we found that TIIA regulated several cellular processesingastric cancer cells, such astranscription mRNA processing, DNA damage and protein unfolding response. Finally, we further validated that TIIA caused protein unfolding response and DNA damage via inducing ROS production. These findings not only uncover the molecular mechanisms mediated by TIIA but also contribute to the development of gastric cancer therapy.
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.
Project description:Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut-brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation.
Project description:In the present investigation, an experimental model of endothelial cell injury was established by subjecting RRAECs to Ang II (5×10-7mol/L) for a duration of 24 h. Subsequently, this model was treated with a combination of Calycosin (3mg/L) and Tanshinone II (3mg/L). The changes in total ATP levels and autophagy function in RRAECs were evaluated using the ATP assay and dansylcadaverine (MDC) staining, respectively. Annexin V-FITC/PI staining and transwell assay were utilized to quantify the apoptosis rate and migration function of RRAECs. Moreover, the utilization of RNA-sequencing technology facilitated the identification of differentially expressed (DE) lncRNAs and mRNAs between various groups. Subsequently, a coexpression network between DE lncRNAs and mRNAs was constructed, followed by the implementation of GO and KEGG pathway enrichment analyses to elucidate the functional implications of the DE mRNAs interacting with lncRNAs within this network.