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:Thermal ablation offers minimally invasive treatment options for hepatocellular carcinoma (HCC) therapy. However, local recurrence due to sublethal temperatures enhances tumor cell survival. This study aims to investigate the tumor-promoting effects of hyperthermia on HCC cells, the role of tanshinone IIA (Tan IIA) in mitigating these effects, and the underlying mechanisms involved. We observed that temperature at 44 °C increased the aggressiveness of HCC cells, and Tan IIA inhibited cell viability and cell invasion, and induced cell cycle arrest and apoptosis of heat-pretreated HCC cells. ALDH7A1 was identified as a target of Tan IIA, and its altered expression resulted in dysregulation of cell viability, invasion, apoptosis, ATP production, glycolysis, osmolyte levels, and reactive oxygen species (ROS). Under hyperosmotic conditions, ALDH7A1 knockdown sensitized heated Huh-7 cells, while its overexpression promoted cell survival and invasion, with corresponding changes in energy metabolism and enzymatic products. Tan IIA and the specific ALDH7A1 inhibitor, 4-diethylaminobenzaldehyde, demonstrated similar effects on gene expression patterns, glycolysis, osmotic regulation, and ROS levels in heated Huh-7 cells. Moreover, Tan IIA is able to direct interact with ALDH7A1 protein. In vitro, Tan IIA combined with hyperosmotic stress significantly inhibited cell invasion and induced apoptosis in heat-induced Huh-7 cells and ALDH7A1 overexpression partially reversed the effects of Tan IIA. In vivo, Tan IIA combined with hyperosmotic stress or glycolysis inhibitor yielded better therapeutic efficacy for HCC. In conclusion, Tan IIA sensitizes HCC cells to sublethal heat by targeting ALDH7A1, leading to disrupted glycolytic and osmolytic balance, subsequently hindering tumor cell survival and increasing apoptosis. These findings highlight a potentially novel strategy for preventing or treating recurrent HCC post-thermal ablation using Tan IIA with hyperosmotic reagents.
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:our study employed a combined proteomic and glycoproteomic approach to investigate the role of protein glycosylation in lipopolysaccharide (LPS)-induced neuroinflammation models. Bioinformatics analysis of the proteomic and glycoproteomic data further emphasized a strong connection between our observed changes and pathways implicated in glycosylation and neuroinflammation. Our findings revealed an overall increase in protein glycosylation levels during neuroinflammatory processes. Crucially, we demonstrated that the pan-glycosylation inhibitor NGI-1 effectively suppressed the inflammatory response in BV2 microglia cells. Building on these findings and leveraging the proteomic and glycoproteomic data from LPS-induced models, we subsequently screened Tanshinone IIA (STS), a bioactive component of Salvia miltiorrhiza (Danshen), identifying it as a potent therapeutic candidate for neuroinflammatory disorders. Tanshinone IIA effectively attenuated aberrant protein glycosylation by reducing glycan occupancy. Mechanistically, this modulatory effect likely involves influencing UDP-GlcNAc levels within the glycosylation biosynthesis pathway and impacting N-acetylaspartate metabolism, thereby disrupting aberrant protein glycosylation and consequently alleviating the inflammatory response. Collectively, our findings offer novel insights into the therapeutic potential of targeting glycosylation modifications in neuroinflammation.
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.