Hydrogen peroxide-mediated oxidative stress and collagen synthesis in cardiac fibroblasts: Blockade by tanshinone IIA

Wang, Ping; Zhou, Sigui; Xu, Li; Lu, Yao; Yuan, Xi; Zhang, Huijie; Li, Ruifang; Fang, Jian; Liu, Peiqing

doi:10.1016/j.jep.2012.10.044

Cited by 39 publications

(21 citation statements)

References 32 publications

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“…CASP1 (22), HIF1A (23), COL1A1 (24) and MT3 were all upregulated by the combined treatments (data not shown). In the drug metabolism array, only two genes, lactoperoxidase (LPO) and amiloride binding protein 1 (ABP1) were upregulated to higher levels by the combined treatments than by each individual modality (Fig.…”

Section: Resultsmentioning

confidence: 92%

Contribution of Dual Oxidase 2 (DUOX2) to Hyper-Radiosensitivity in Human Gastric Cancer Cells

et al. 2015

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Whole-abdominal radiotherapy (WART) is a primary method for managing gastrointestinal cancers that have disseminated into intra-abdominal tissues. While effective, this approach is limited because of the increased toxicity to normal tissue associated with combined WART and full-dose chemotherapy regimens. Recent studies have demonstrated a survival advantage in a novel treatment paradigm that allows for the safe use of full-dose systemic chemotherapy in combination with low-dose fractionated radiotherapy (LDFRT). Traditionally, radiation doses greater than 120 cGy have been used in radiotherapy because lower doses were thought to be ineffective for tumor therapy. However, we now know that LDFRT can produce hyper-radiosensitivity (HRS), a phenomenon where cells undergo apoptosis at radiation doses as low as 15 cGy, in a number of proliferating cells. The objectives of our current study were to determine whether LDFRT can induce HRS in gastrointestinal cancer cells and to identify biomarkers of chemopotentiation by LDFRT. Our data indicate that three consecutive daily fractions of 15 cGy produced HRS in gastric cancer cells and potentiated a modified regimen of docetaxel, cisplatin and 5′-fluorouracil (mDCF). Colony survival assays indicated that 15 cGy was sufficient to kill 90% of the cells when LDFRT was combined with mDCF whereas a dose almost 10 times higher (135 cGy) was needed to achieve the same rate when using conventional radiotherapy alone. RT2 PCR Profiler™ array analysis indicated that this combined regimen upregulated dual oxidase 2 (DUOX2), an enzyme functioning in the production of hydrogen peroxide, without upregulating genes involved in DNA repair. Moreover, downregulation of DUOX2 increased radioresistance at every radiation dose tested. In addition, our data indicate that reactive oxygen species (ROS) increase up to 3.5-fold in cells exposed to LDFRT and mDCF. Furthermore, inhibition of NADPH oxidase abrogated the killing efficiency of this combined regimen. Taken together these data suggest that chemopotentiation by LDFRT in gastric cancer cells may be due, at least in part, to increased ROS production (DUOX2) without upregulation of the DNA repair machinery. These data thus provide a rationale for further explorations of potential clinical applications of LDFRT, such as in WART, as a chemopotentiator for advanced and metastatic gastric cancers.

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Section: Resultsmentioning

confidence: 92%

Contribution of Dual Oxidase 2 (DUOX2) to Hyper-Radiosensitivity in Human Gastric Cancer Cells

et al. 2015

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“…Tanshinone IIA has been shown to possess a variety of biological activities in the cardiovascular system, such as antioxidant, anticoagulant, anti-atherosclerotic, anti-apoptotic and antihypertrophic activities (14)(15)(16)(17). Tanshinone IIA has also been shown to possess anti-fibrotic activities (18,19). In the present study, we explored the effects and mechanisms of action of STS on the TGF-β1-induced collagen expression and differentiation of atrial fibroblasts into myofibroblasts in vitro, demonstrating the potential application of STS in clinical practice for the treatment of atrial fibrosis and AF.…”

Section: Introductionmentioning

confidence: 99%

Sodium tanshinone IIA sulfonate attenuates the transforming growth factor-β1-induced differentiation of atrial fibroblasts into myofibroblasts in vitro

Liu

Hao

et al. 2015

International Journal of Molecular Medicine

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The differentiation of atrial fibroblasts into myofibroblasts is a critical event in atrial fibrosis. One of the most important factors in atrial fibroblast differentiation is transforming growth factor-β1 (TGF-β1). Accumulating evidence indicates that sodium tanshinone IIA sulfonate (STS) possesses antifibrotic properties. In this study, we therefore investigated whether STS attenuates the TGF-β1‑induced differentiation of atrial fibroblasts. TGF-β1 enhanced collagen production, collagen synthesis and the expression of collagen type I and III, as shown by hydroxyproline assay, collagen synthesis assay and western blot analysis, respectively. In addition, as shown by immunohistochemistry and western blot analysis, TGF-β1 enhanced the expression of α-smooth muscle actin (α-SMA), which is the hallmark of myofibroblast differentiation. These responses were attenuated by treatment with STS. In addition, STS suppressed the TGF-β1‑induced expression of phosphorylated (p)Smad/pSmad3 expression and nuclear translocation. Furthermore, STS suppressed extracellular signal-regulated kinase (ERK) phosphorylation. In conclusion, the current study demonstrates that STS exerts antifibrotic effects by modulating atrial fibroblast differentiation through ERK phosphorylation and the Smad pathway.

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“…Tanshinone IIA prevents cardiac fibroblast proliferation by interfering with the generation of reactive oxygen species (ROS) and involves the activation of the endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway [21]. Tanshinone IIA can also inhibit H 2 O 2 -induced collagen synthesis via attenuation of O 2 − -generation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity [22]. Paeonol suppresses vascular smooth muscle cell proliferation in vivo and in vitro, which might be related to a decrease in lipid content, lipid peroxidation, and proinflammatory cytokine concentrations.…”

Section: Discussionmentioning

confidence: 99%

Yiqihuoxuejiedu Formula Inhibits Vascular Remodeling by Reducing Proliferation and Secretion of Adventitial Fibroblast after Balloon Injury

Zhao

Wang

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Vascular remodeling occurs in atherosclerosis, hypertension, and restenosis after percutaneous coronary intervention. Adventitial remodeling may be a potential therapeutic target. Yiqihuoxuejiedu formula uses therapeutic principles from Chinese medicine to supplement Qi, activate blood circulation, and resolve toxin and it has been shown to inhibit vascular stenosis. To investigate effects and mechanisms of the formula on inhibiting vascular remodeling, especially adventitial remodeling, rats with a balloon injury to their common carotid artery were used and were treated for 7 or 28 days after injury. The adventitial area and α-SMA expression increased at 7 days after injury, which indicated activation and proliferation of adventitial fibroblasts. Yiqihuoxuejiedu formula reduced the adventitial areas at 7 days, attenuated the neointima and vessel wall area, stenosis percent, and α-SMA expression in the neointima, and reduced collagen content and type I/III collagen ratio in the adventitia at 28 days. Yiqihuoxuejiedu formula had more positive effects than Captopril in reducing intimal proliferation and diminishing stenosis, although Captopril lowered neointimal α-SMA expression and reduced the collagen content at 28 days. Yiqihuoxuejiedu formula has inhibitory effects on positive and negative remodeling by reducing adventitial and neointimal proliferation, reducing content, and elevating adventitial compliance.

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Hydrogen peroxide-mediated oxidative stress and collagen synthesis in cardiac fibroblasts: Blockade by tanshinone IIA

Cited by 39 publications

References 32 publications

Contribution of Dual Oxidase 2 (DUOX2) to Hyper-Radiosensitivity in Human Gastric Cancer Cells

Contribution of Dual Oxidase 2 (DUOX2) to Hyper-Radiosensitivity in Human Gastric Cancer Cells

Sodium tanshinone IIA sulfonate attenuates the transforming growth factor-β1-induced differentiation of atrial fibroblasts into myofibroblasts in vitro

Yiqihuoxuejiedu Formula Inhibits Vascular Remodeling by Reducing Proliferation and Secretion of Adventitial Fibroblast after Balloon Injury

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