scholarly journals Tanshinones induce tumor cell apoptosis via directly targeting FHIT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianglian Zhou ◽  
Yuting Pan ◽  
Yue Wang ◽  
Bojun Wang ◽  
Yu Yan ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Binding Affinities ◽  
Tumor Cell Apoptosis ◽  
Anti Cancer ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Direct Binding ◽  
Fhit Protein ◽  
Diadenosine Triphosphate

AbstractThe liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

Tanshinones: An update in the medicinal chemistry in recent 5 years

2020 ◽  
Vol 27 ◽  
Author(s):  
Zhencheng Lai ◽  
Jixiao He ◽  
Changxin Zhou ◽  
Huajun Zhao ◽  
Sunliang Cui
Keyword(s):  
Structural Modification ◽  
Salvia Miltiorrhiza ◽  
Antibacterial Activities ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Salvia Miltiorrhiza Bunge ◽  
Anticancer Activities ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Antiviral Activities ◽  
Cardioprotective Effects

: Tanshinones is an important type of natural products isolated from Salvia miltiorrhiza Bunge with various bioactivities. Tanshinone IIa, cryptotanshinone and tanshinone I are three kinds of tanshinones which have been widely investigated. Particularly, sodium tanshinone IIa sulfonate is a water-soluble derivative of tanshinone IIa and it is used in clinical in China for treating cardiovascular diseases. In recent years, there are increasing interests for investigation of tanshinones derivatives in various diseases. This article present a review of the anti-atherosclerotic effects, cardioprotective effects, anticancer activities, antibacterial activities and antiviral activities of tanshinones and structural modification work in recent years.

scholarly journals Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tangting Chen ◽  
Miaoling Li ◽  
Xuehui Fan ◽  
Jun Cheng ◽  
Liqun Wang
Keyword(s):  
Angiotensin Ii ◽  
Critical Role ◽  
Water Soluble ◽  
Collagen I ◽  
Tanshinone Iia ◽  
Ang Ii ◽  
Induced Differentiation ◽  
Fibroblast Migration ◽  
Collagen Iii ◽  
Sodium Tanshinone Iia Sulfonate

Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence of DS-201. Then, α-smooth muscle actin (α-SMA), collagen I, and collagen III expression and reactive oxygen species (ROS) generation were measured. The expression of transforming growth factor-β1 (TGF-β1) and the downstream signaling of TGF-β1, such as phosphorylation of Smad2/3, were also determined. The results demonstrated that DS-201 significantly prevented Ang II-induced human atrial fibroblast migration and decreased Ang II-induced α-SMA, collagen I, and collagen III expression. Furthermore, increased production of ROS and expression of TGF-β1 stimulated by Ang II were also significantly inhibited by DS-201. Consistent with these results, DS-201 significantly inhibited Ang II-evoked Smad2/3 phosphorylation and periostin expression. These results and the experiments involving N-acetyl cysteine (antioxidant) and an anti-TGF-β1 antibody suggest that DS-201 prevent Ang II-induced differentiation of atrial fibroblasts to myofibroblasts, at least in part, through suppressing oxidative stress and inhibiting the activation of TGF-β1 signaling pathway. All of these data indicate the potential utility of DS-201 for the treatment of cardiac fibrosis.

scholarly journals Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Lunjie Lu ◽  
Jun Zhou ◽  
Jingying Zhang ◽  
Jun Che ◽  
Yang Jiao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Sodium Sulfonate ◽  
Pharmacologically Active ◽  
Magnesium Isoglycyrrhizinate

Tanshinone IIA sodium sulfonate (TSS) is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI) in D-galactosamine- (D-Gal-) induced acute liver injury (ALI) in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.

Tanshinone IIA: New Perspective on the Anti-Tumor Mechanism of A Traditional Natural Medicine

2022 ◽  
pp. 1-31
Author(s):  
Wenfeng Zhang ◽  
Cun Liu ◽  
Jie Li ◽  
Yiping Lu ◽  
Huayao Li ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Cell ◽  
Cell Apoptosis ◽  
Salvia Miltiorrhiza ◽  
Tanshinone Iia ◽  
Migration And Invasion ◽  
Jnk Pathway ◽  
Tumor Cell Apoptosis ◽  
Chemotherapy Drugs ◽  
Natural Medicine

The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza. Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

2015 ◽  
Vol 308 (3) ◽  
pp. R163-R172 ◽  
Author(s):  
Jude S. Morton ◽  
Anita Quon ◽  
Po-Yin Cheung ◽  
Tatsuya Sawamura ◽  
Sandra T. Davidge
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Rat Model ◽  
Salvia Miltiorrhiza ◽  
Oxidized Ldl ◽  
Maternal Blood ◽  
Tanshinone Iia ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Paf Receptor ◽  
Maternal Blood Pressure

Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure.

scholarly journals Tanshinone IIA: A Promising Natural Cardioprotective Agent

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Qinghua Shang ◽  
Hao Xu ◽  
Li Huang
Keyword(s):  
Myocardial Infarction ◽  
Angina Pectoris ◽  
Salvia Miltiorrhiza ◽  
Tanshinone Iia ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Cardioprotective Effects

Tanshinone IIA (Tan IIA) is a member of the major lipophilic components extracted from the root ofSalvia miltiorrhizaBunge, which is currently used in China and other neighboring countries to treat patients suffering from myocardial infarction (MI), angina pectoris, stroke, diabetes, sepsis, and other conditions. However, Tan IIA is not easy to be absorbed through intestinal pathway. To raise the bioavailability of the herb, sodium tanshinone IIA sulfonate (STS) was developed. This paper discussed the pharmacology of Tan IIA, STS, and their potential cardioprotective effects.

scholarly journals Tanshinone IIA induces ferroptosis in gastric cancer cells through p53-mediated SLC7A11 down-regulation

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Zhenhua Guan ◽  
Jing Chen ◽  
Xueliang Li ◽  
Na Dong
Keyword(s):  
Gastric Cancer ◽  
Lipid Peroxidation ◽  
Cancer Cells ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Tanshinone Iia ◽  
Gastric Cancer Cells ◽  
P53 Expression ◽  
Anti Cancer ◽  
Pharmacologically Active

Abstract Gastric cancer represents a malignant type of cancer worldwide. Tanshinone IIA (Tan IIA), a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge (Danshen), has been reported to possess an anti-cancer effect in gastric cancer. However, its mechanisms are still not fully understood. In the present study, we found that Tan IIA induced ferroptosis in BGC-823 and NCI-H87 gastric cancer cells. Tan IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of lipid peroxidation, inhibited Tan IIA caused-lipid peroxidation and Ptgs2 and Chac1 expression. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Tan IIA caused decreased intracellular glutathione (GSH) level and cysteine level and increased intracellular reactive oxygen species (ROS) level. p53 knockdown attenuated Tan IIA-induced lipid peroxidation and ferroptosis. Tan IIA also induced lipid peroxidation and ferroptosis in BGC-823 xenograft model, and the anti-cancer effect of Tan IIA was attenuated by Fer-1 in vivo. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Our study have identified a novel mechanism of Tan IIA against gastric cancer, and might provide a critical insight into the application of Tan IIA in gastric cancer intervention.

Tanshinone IIA Alleviates Pirarubicin-Induced Cytotoxicity in H9c2 Cardiomyocytes via Regulation of Hippo Signaling Pathway

2020 ◽  
Vol 10 (5) ◽  
pp. 647-653
Author(s):  
Jingping Lu ◽  
Ning Liu ◽  
Xiaofan Miao ◽  
Ran Chen ◽  
Boqian Zhu
Keyword(s):  
Salvia Miltiorrhiza ◽  
Hippo Pathway ◽  
Critical Role ◽  
Tanshinone Iia ◽  
Cancer Drug ◽  
Hippo Signaling ◽  
Incidence And Mortality ◽  
Anti Cancer ◽  
H9c2 Cardiomyocytes ◽  
The Relationship

Malignant tumor is considered as one of the fatal diseases worldwide with high incidence and mortality. Pirarubicin (THP) is an anti-cancer drug commonly used in the treatment of patients with malignancies. In view of that THP exists the cardiotoxic effects, its clinical application is restricted. Tanshinone IIA (TSA) is a core active monomer drawn from Salvia miltiorrhiza that possesses the cardioprotective properties. In the present study, we proposed to unveil the potential and latent mechanism of TSA in the cardiotoxicity caused by THP. Our results validated that THP treatment gave rise to the injury of cardiomyocytes. Moreover, administration of TSA abrogated the impacts of THP on H9c2 cells. A myriad of literatures demonstrate that Hippo pathway plays a critical role in the development of multiple cardiovascular disorders. Hence, we further explored the relationship between TSA and Hippo pathway. It was proven that THP contributed to the activation of Hippo pathway and TSA treatment inhibited Hippo pathway. More importantly, we revealed that TSA attenuated THP-mediated cytotoxicity in cardiomyocytes through modulating Hippo pathway, which provide insights into the improvement of THP-induced toxic and side effects.

scholarly journals An overview of the anti-cancer actions of Tanshinones, derived from Salvia miltiorrhiza (Danshen)

2020 ◽  
Vol 1 (3) ◽  
Author(s):  
Irum Naz ◽  
Myriam Merarchi ◽  
Shanaya Ramchandani ◽  
Muhammad Rashid Khan ◽  
Muhammad Nouman Malik ◽  
...  
Keyword(s):  
Prostate Cancer Cell ◽  
Salvia Miltiorrhiza ◽  
Cancer Therapeutics ◽  
Review Article ◽  
Tanshinone Iia ◽  
Pharmacological Effects ◽  
Medicinal Compound ◽  
Anti Cancer ◽  
Herbal Medicinal ◽  
Clinical Potential

Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented.

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